ANTIVIRAL PRODRUGS AND FORMULATIONS THEREOF CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims priority to U.S. provisional patent application No. 63/412,961, which was filed on October 4, 2022, and which is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION [0002] This disclosure relates to antiviral compounds and compositions thereof useful for the treatment and/or prevention of various viral infections, such as SARS-CoV-2 infections. BACKGROUND OF THE INVENTION [0003] Nucleoside analogs have been utilized as small-molecule, broad-spectrum, direct- acting antivirals for the prevention and treatment of viral infections. For RNA viruses, such compounds target the RNA-dependent RNA polymerase (RDRP) which carries out the key viral RNA synthesis reactions. RDRPs are attractive drug targets because they are essential for virus growth, are not encoded by the mammalian host cell and are well-conserved among viral families. For SARS-CoV-2 the RDRP is non-structural protein (nsp) 12. Nsp12 associates with nsp7 and nsp8 in order to replicate the SARS-COV-2 genome. To date, nucleoside analogs that selectively target the RDRP have been the most promising approach to SARS-CoV-2 inhibition. Currently, there are ribonucleoside analogs that are approved by a stringent regulatory authority; such as Remdesivir (RDV; GS-5734, registered by Gilead Sciences as VEKLURY) (whose structure is show below) and are undergoing mid-stage clinical development, for the treatment of SARS-CoV-2 infections. [0004] Remdesivir functions as a non-obligate or delayed RNA chain terminator. Delayed chain termination occurs when a nucleotide analogue has a free 3-OH group required for the addition of natural nucleotides. The incorporation of the delayed chain terminator, however, perturbs the RNA structure, and RNA synthesis is halted. In SARS- CoV-1, SARS-CoV-2, and MERS-CoV, remdesivir-TP incorporation consistently results in chain termination. Remdesivir (RDV, GS-5374), a nucleotide analog prodrug and an RNA- dependent RNA polymerase (RdRp) inhibitor with broad antiviral activity, demonstrated positive clinical endpoints in a Phase III Adaptive COVID-19 Treatment Trial (median time to recovery shortened from 15 to 11 days) that justified its emergency use authorization by the US Food & Drug Administration for treatment of hospitalized COVID-19 patients. However, its intravenous delivery makes the discovery of new or supplemental therapies that produce greater clinical improvements and can be administered outside of a hospital setting (i.e. orally) highly desirable. As mentioned, RDV is administered intravenously due to the drug’s poor hepatic stability and low plasma/serum stability, with each infusion taking up to two hours and requiring daily administration for either 5 or 10 days. Accordingly, alternative therapies that improve oral exposure is desirable. The present invention provides such alternatives via making prodrugs of parent nucleoside GS-441524. [0005] Currently there are only two COVID-19 RdRp inhibitors approved by FDA for EUA. While Remdesivir is limited by IV dosing, molnupiravir has shown signs of long-term toxicity due to its mutagenic nature. Hence, an oral prodrug of GS-441524 provides an excellent opportunity to fill the gap and work as companion drug to a protease inhibitor to combat resistance. Thus, there exists a need in the field for more efficacious COVID-19 RdRp inhibitors with better toxicity profiles. BRIEF DESCRIPTION OF THE FIGURES [0006] Figure 1. PBMC Concentration of Triphosphates (nM) vs. Time (h) compared to Remdesivir. [0007] Figure 2. XPRD of sacchrinate salt of compound 1. [0008] Figure 3. TGA and DSC of sacchrinate salt of compound 1. SUMMARY OF THE INVENTION [0009] The application provides compounds of Formula (I) suitable for oral administration as improved treatments for viral infections caused by SARS-COV-2, including COVID-19 viral infections, as exemplified by Compound 1 which shows ~3-fold increase in dose-normalized (DN) area under curve (AUC) exposure of GS-441524-TP levels than known prodrug GS-621763 (Fig.1). [0010] The application provides compounds of Formulae (I-IX)

wherein all variables including instances of are as defined hereinbelow. [0011] The application further provides pharmaceutical compositions comprising a compound of any one of Formulae I-IX, admixed with a pharmaceutically acceptable carrier, diluent, or excipient. [0012] The application further provides the above pharmaceutical compositions, further comprising one or more therapeutic compounds or compositions. [0013] The application further provides the above pharmaceutical compositions, wherein the one or more therapeutic compounds or compositions is a second antiviral compound or composition. [0014] The application further provides the above pharmaceutical compositions, wherein the second antiviral compound or composition is remdesivir or molnupiravir. [0015] The application further provides methods of inhibiting an RNA-dependent RNA polymerase, comprising administering to a subject patient infected with a virus a therapeutically effective amount of a compound of any one of Formulae I-IX or a pharmaceutical composition comprising a compound of any one of Formulae I-IX. [0016] The application further provides a method of inhibiting an RNA-dependent RNA polymerase, comprising administering to a subject patient infected with a virus a therapeutically effective amount of a compound of any one of Formulae I-IX or a pharmaceutical composition comprising a compound of any one of Formulae I-IX. [0017] The application further provides a method of preventing, ameliorating, or treating an RNA viral infection, comprising administering to a subject in need thereof a therapeutically effective amount of the compound a compound of any one of Formulae I-IX or a pharmaceutical composition comprising a compound of any one of Formulae I-IX. [0018] The application further provides the above method, wherein the RNA viral infection is caused by SARS-COV-2. DETAILED DESCRIPTION OF THE INVENTION [0019] The application provides compounds of Formulae (I-IX)

wherein all variables including instances of are as defined hereinbelow. [0020] The application provides the following Embodiments: Embodiments [0021] Embodiment 1. A compound of Formula (I) wherein: X ¹ is O, CH ₂ , CH((C ₁ -C ₆ )alkyl), CH(NH ₂ ), CH((C ₁ -C ₆ )heteroalkyl), CH((C ₁ -C ₆ )haloalkyl), CH((C ₃ -C ₇ )cycloalkyl), CH((C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl), CH((C ₃ -C ₇ )heterocycloalkyl), CH((C ₁ -C ₆ )alkyl (C ₃ -C ₇ )heterocycloalkyl), CH((C ₆ -C ₁₀ )aryl), CH((C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), CH((C ₅ -C ₁₀ )heteroaryl), or CH((C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl); X ² is O, CH ₂ , CH((C ₁ -C ₆ )alkyl), CH(NH ₂ ), CH((C ₁ -C ₆ )heteroalkyl), CH((C ₁ -C ₆ )haloalkyl), CH((C ₃ -C ₇ )cycloalkyl), CH((C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl), CH((C ₃ -C ₇ )heterocycloalkyl), CH((C ₁ -C ₆ )alkyl (C ₃ -C ₇ )heterocycloalkyl), CH((C ₆ -C ₁₀ )aryl), CH((C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), CH((C ₅ -C ₁₀ )heteroaryl), or CH((C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl); represents a 4- to 14-membered saturated or partially saturated alkyl or heteroalkyl chain, optionally substituted with one or more Y; each Y is independently -OH, -O(C ₁ -C ₆ )alkyl, -SH, -S(C ₁ -C ₆ )alkyl, -NH ₂ , -NH(C ₁ - C ₆ )alkyl, -N((C ₁ -C ₆ )alkyl) ₂ , halo, -CN, -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ - C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, - (C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)(C ₁ - C ₆ )alkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)(C ₆ -C ₁₀ )aryl, - C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)(C ₅ -C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, -C(=O)OH, -C(=O)O(C ₁ -C ₆ )alkyl, -C(=O)O(C ₁ -C ₆ )heteroalkyl, -C(=O)O(C ₃ - C ₇ )cycloalkyl, -C(=O)O(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₅ -C ₁₀ )heteroaryl, -C(=O)O(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - C(=O)NH(C ₁ -C ₆ )alkyl, -C(=O)NH(C ₁ -C ₆ )heteroalkyl, -C(=O)NH(C ₃ -C ₇ )cycloalkyl, - C(=O)NH(C ₃ -C ₇ )heterocycloalkyl, -C(=O)NH(C ₆ -C ₁₀ )aryl, -C(=O)NH(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -C(=O)NH(C ₅ -C ₁₀ )heteroaryl, -C(=O)NH(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - S(=O) ₂ (C ₁ -C ₆ )alkyl, -P(=O)(OH) ₂ , -P(=O)(OH)(O(C ₁ -C ₆ )alkyl),-P(=O)(O(C ₁ -C ₆ )alkyl) ₂ , - P(=O)(OH)(O(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ -C ₁₀ )aryl) ₂ , -P(=O)(OH)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl) ₂ , - P(=O)(OH)(NH(C ₁ -C ₆ )alkyl),-P(=O)(NH(C ₁ -C ₆ )alkyl) ₂ , -P(=O)(OH)(NH(C ₆ -C ₁₀ )aryl), - P(=O)(O(C ₁ -C ₆ )alkyl)(NH(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₆ -C ₁₀ )aryl) ₂ , -P(=O)(OH)(NH(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ - C ₁₀ )aryl)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl) ₂ , - P(=O)(NH ₂ )(O(C ₁ -C ₆ )alkyl), -P(=O)(NH ₂ )(O(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl)(O(C ₆ - C ₁₀ )aryl), -P(=O)(NH ₂ )(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl)(O(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), or - P(=O)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl); R ¹ is H or selected from the group consisting of -C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ - C ₆ )heteroalkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ - C7)heterocycloalkyl, -C(=O)(C ₁ -C ₆ )alkyl(C3-C7)heterocycloalkyl, -C(=O)(C6-C10)aryl, - C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)(C ₅ -C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl, - C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl, -P(=X)(OR ^1’ )NH(C ₃ -C ₇ )cycloalkyl, -P(=X)(OR ^1’ )NH(C ₃ - C ₇ )heterocycloalkyl, -P(=X)(OR ^1’ )NH(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₅ -C ₁₀ )heteroaryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, -P(=X)(NHR ^1’ )NH(C ₁ -C ₆ )alkyl, -P(=X)(NHR ^1’ )NH(C ₁ -C ₆ )heteroalkyl, - P(=X)(NHR ^1’ )NH(C ₁ -C ₆ )haloalkyl, -P(=X)(NHR ^1’ )NH(C3-C7)cycloalkyl, - P(=X)(NHR ^1’ )NH(C ₃ -C ₇ )heterocycloalkyl, -P(=X)(NHR ^1’ )NH(C ₆ -C ₁₀ )aryl, - P(=X)(NHR ^1’ )NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -P(=X)(NHR ^1’ )NH(C ₅ -C ₁₀ )heteroaryl, - P(=X)(NHR ^1’ )NH(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O- (C ₁ -C ₆ )alkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )heteroalkyl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl- C(=O)O-(C ₃ -C ₇ )cycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O- (C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -P(=X)(OR ^1’ )NH(C ₁ - C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ - C ₆ )heteroalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₃ -C ₇ )cycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ - C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl- C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ - C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ - C ₆ )heteroalkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )heteroalkyl-C(=O)O- (C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )heteroalkyl, -P(=X)(OR ^1’ )NH(C ₁ - C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₃ - C ₇ )cycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ - C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -P(=X)(OR ^1’ )NH(C ₁ - C ₆ )haloalkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, and - P(=X)(OR ^1’ )NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, wherein each instance of -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ - C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ -C ₆ )heteroalkynyl, -(C ₂ - C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -(C ₃ - C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl is optionally and independently substituted with one or more -OH, -NH ₂ , halo, -CN, -(C ₁ -C ₆ )alkyl, -(C ₁ - C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ - C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ - C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, -(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ - C ₇ )heterocycloalkyl, -C(=O)(C ₆ -C ₁₀ )aryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)(C ₅ - C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)OH, -C(=O)O(C ₁ -C ₆ )alkyl, - C(=O)O(C ₁ -C ₆ )heteroalkyl, -C(=O)O(C ₃ -C ₇ )cycloalkyl, -C(=O)O(C ₃ -C ₇ )heterocycloalkyl, - C(=O)O(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₅ -C ₁₀ )heteroaryl, - C(=O)O(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)NH(C ₁ -C ₆ )alkyl, -C(=O)NH(C ₁ - C ₆ )heteroalkyl, -C(=O)NH(C ₃ -C ₇ )cycloalkyl, -C(=O)NH(C ₃ -C ₇ )heterocycloalkyl, - C(=O)NH(C ₆ -C ₁₀ )aryl, -C(=O)NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)NH(C ₅ -C ₁₀ )heteroaryl, or -C(=O)NH(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl; each X is independently O or S; each R ^1’ is independently H or selected from the group consisting of -(C ₁ -C ₆ )alkyl, -(C ₁ - C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ - C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ - C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ - C6)alkyl(C ₅ -C ₁₀ )heteroaryl, wherein each is optionally and independently substituted with one or more -OH, -O(C ₁ -C ₆ )alkyl, -SH, -S(C ₁ -C ₆ )alkyl, -NH ₂ , -NH(C ₁ -C ₆ )alkyl, -N((C ₁ - C ₆ )alkyl) ₂ , halo, -CN, -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ -C ₆ )heteroalkynyl, -(C ₂ - C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -(C ₃ - C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)(OH), -C(=O)O(C ₁ - C ₆ )alkyl, -C(=O)O(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -S(=O) ₂ (C ₁ -C ₆ )alkyl, - P(=O)(OH) ₂ , -P(=O)(OH)(O(C ₁ -C ₆ )alkyl),-P(=O)(O(C ₁ -C ₆ )alkyl) ₂ , -P(=O)(OH)(O(C ₆ - C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ -C ₁₀ )aryl) ₂ , - P(=O)(OH)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)((C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), or -P(=O)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl) ₂ ; R ² is H or selected from the group consisting of -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C1- C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, - (C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ -C ₆ )heteroalkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₁ - C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )heterocycloalkyl, -C(=O)(C ₆ -C ₁₀ )aryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)(C ₅ - C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl, - C(=O)CH(NH ₂ )(C ₃ -C ₇ )cycloalkyl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )cycloalkyl, - C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₃ -C ₇ )cycloalkyl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl)(C ₃ - C ₇ )cycloalkyl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )cycloalkyl, - C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )cycloalkyl, -C(=O)CH(NH ₂ )(C ₃ - C ₇ )heterocycloalkyl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(N((C ₁ - C ₆ )alkyl) ₂ )(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(N((C ₁ - C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(NH ₂ )(C ₆ -C ₁₀ )aryl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₆ -C ₁₀ )aryl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₆ -C ₁₀ )aryl, - C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)CH(NH ₂ )(C ₅ - C ₁₀ )heteroaryl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(N((C ₁ - C ₆ )alkyl) ₂ )(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ -C ₆ )alkyl, -C(=O)O-(C ₁ -C ₆ )heteroalkyl, -C(=O)O- (C ₁ -C ₆ )haloalkyl, -C(=O)O-(C ₃ -C ₇ )cycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, - C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O- (C ₆ -C ₁₀ )aryl, -C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)O-(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -C(=O)O-(C ₁ - C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )heteroalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, - C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ -C ₇ )cycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ - C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, - C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl- C(=O)O-(C ₆ -C ₁₀ )aryl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)O- (C ₁ -C ₆ )alkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, wherein each instance of -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ - C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, - (C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl is optionally and independently substituted with one or more -OH, -NH ₂ , halo, -CN, -(C ₁ - C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, - (C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl-(C ₃ - C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, or -(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl; including enantiomers, racemic and scalemic mixtures, and pharmaceutically acceptable salts thereof. [0022] Embodiment 2. The compound of Embodiment 1, having Formula (II) wherein: X ¹ and X ² are both O, CH ₂ , CH((C ₁ -C ₆ )alkyl), or CH(NH ₂ ); and R ¹ is H or selected from the group consisting of -C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ -C ₆ )alkyl(C ₆ - C10)aryl, -C(=O)(NH2)(C ₁ -C ₆ )alkyl, or -P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl, - P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, and -P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl- C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, each optionally and independently substituted by one or more R ^1’ . [0023] Embodiment 3. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is H. [0024] Embodiment 4. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -C(=O)(C ₁ -C ₆ )alkyl. [0025] Embodiment 5. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -C(=O)i-Pr. [0026] Embodiment 6. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl optionally substituted with one or more R ^1’ . [0027] Embodiment 7. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -C(=O)CH ₂ Ph optionally substituted with one or more R ^1’ . [0028] Embodiment 8. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -C(=O)(NH ₂ )(C ₁ -C ₆ )alkyl optionally substituted with one or more R ^1’ . [0029] Embodiment 9. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -C(=O)(NH ₂ )i-Pr. [0030] Embodiment 10. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl optionally substituted with one or more R ^1’ . [0031] Embodiment 11. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -P(=O)(OR ^1’ )NH(Me)C(=O)O-(C ₁ -C ₆ )alkyl optionally substituted with one or more R ^1’ . [0032] Embodiment 12. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -P(=O)(OR ^1’ )NH(Me)C(=O)O-2-ethylbutyl optionally substituted with one or more R ^1’ . [0033] Embodiment 13. The compound of either Embodiment 1 or Embodiment 2, wherein R ¹ is -P(=O)(OR ^1’ )NH((C ₁ -C ₆ )alkyl)C(=O)O-2-ethylbutyl optionally substituted with one or more R ^1’ . [0034] Embodiment 14. The compound of Embodiment 1, having Formula (III)

wherein: represents either a single or double bond; L ¹ and L ² are independently CH ₂ , CH((C ₁ -C ₆ )alkyl), or S, when is a single bond; or L ¹ and L ² are independently CH or C((C ₁ -C ₆ )alkyl) when is a double bond; m is 0, 1, 2, 3, 4, or 5; and n is 0, 1, 2, 3, 4, or 5. [0035] Embodiment 15. The compound of any one of Embodiments 1-14, having Formula (IV) [0036] Embodiment 16. The compound of any one of Embodiments 1-14, having Formula (V)

[0037] Embodiment 17. The compound of any one of Embodiments 1-14, having Formula (VI) [0038] Embodiment 18. The compound of any one of Embodiments 1-17, wherein X ¹ and X ² are CH ₂ . [0039] Embodiment 19. The compound of any one of Embodiments 1-17, wherein X ¹ and X ² are O. [0040] Embodiment 20. The compound of any one of Embodiments 1-17, wherein X ¹ and X ² are CH((C ₁ -C ₆ )alkyl). [0041] Embodiment 21. The compound of any one of Embodiments 1-17, wherein X ¹ and X ² are CH(Me). [0042] Embodiment 22. The compound of any one of Embodiments 1-17, wherein X ¹ and X ² are CH(NH ₂ ). [0043] Embodiment 23. The compound of any one of Embodiments 14-22, wherein R ¹ H or selected from the group consisting of -C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -C(=O)(NH ₂ )(C ₁ -C ₆ )alkyl, or -P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl, - P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, and -P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl- C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, each optionally and independently substituted by one or more R ^1’ . [0044] Embodiment 24. The compound of Embodiment 23, wherein R ¹ is H. [0045] Embodiment 25. The compound of Embodiment 23, wherein R ¹ is -C(=O)(C ₁ - C ₆ )alkyl optionally substituted with one or more R ^1’ . [0046] Embodiment 26. The compound of Embodiment 25, wherein R ¹ is -C(=O)i-Pr. [0047] Embodiment 27. The compound of Embodiment 23, wherein R ¹ is -C(=O)(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl optionally substituted with one or more R ^1’ . [0048] Embodiment 28. The compound of Embodiment 27, wherein R ¹ is -C(=O)CH ₂ Ph optionally substituted with one or more R ^1’ . [0049] Embodiment 29. The compound of Embodiment 23, wherein R ¹ is - P(=O)(OR ^1’ )NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl optionally substituted with one or more R ^1’ . [0050] Embodiment 30. The compound of Embodiment 29, wherein R ¹ is - P(=O)(OPh)NHCH(Me)C(=O)O-2-ethylbutyl optionally substituted with one or more R ^1’ . [0051] Embodiment 31. The compound of Embodiment 29, wherein R ¹ is -P(=O)(OPh)L- alaninate. [0052] Embodiment 32. The compound of Embodiment 23, wherein R ¹ is - C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl optionally substituted with one or more R ^1’ . [0053] Embodiment 33. The compound of Embodiment 32, wherein R ¹ is - C(=O)CH(NH ₂ )i-Pr. [0054] Embodiment 34. The compound of any one of Embodiments 2-33, wherein m and n are 2, 3, or 6. [0055] Embodiment 35. The compound of Embodiment 34, wherein m and n are 2. [0056] Embodiment 36. The compound of Embodiment 34, wherein m and n are 3. [0057] Embodiment 37. The compound of Embodiment 34, wherein m and n are 6. [0058] Embodiment 38. A compound of Formula (VII) wherein: X is O or S; X ¹ is O, CH ₂ , CH((C ₁ -C ₆ )alkyl), CH(NH ₂ ), CH((C ₁ -C ₆ )heteroalkyl), CH((C ₁ -C ₆ )haloalkyl), CH((C ₃ -C ₇ )cycloalkyl), CH((C ₃ -C ₇ )heterocycloalkyl), CH((C ₆ -C ₁₀ )aryl), CH((C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl), CH((C ₅ -C ₁₀ )heteroaryl), or CH((C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl); L is -(C ₁ -C ₆ )alkyl-O-, -(C ₁ -C ₆ )heteroalkyl-O-, -(C ₁ -C ₆ )haloalkyl-O-, -(C ₂ -C ₆ )alkenyl-O-, - (C2-C6)heteroalkenyl-O-, -(C2-C6)haloalkenyl-O-, -(C2-C6)alkynyl-O-, -(C2-C6)heteroalkynyl- O-, -(C ₂ -C ₆ )haloalkynyl-O-, -(C ₃ -C ₇ )cycloalkyl-O-, -(C ₃ -C ₇ )heterocycloalkyl-O-, -(C ₆ - C ₁₀ )aryl-O-, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl-O-, -(C ₅ -C ₁₀ )heteroaryl-O-, -(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl-O-, each optionally and independently substituted with one or more L’; each L’ is independently -OH, -O(C ₁ -C ₆ )alkyl, -SH, -S(C ₁ -C ₆ )alkyl, -NH ₂ , -NH(C ₁ -C ₆ )alkyl, -N((C ₁ -C ₆ )alkyl) ₂ , halo, -CN, -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ - C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ - C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ - C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - C(=O)OH, -C(=O)O(C ₁ -C ₆ )alkyl, -C(=O)O(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, - S(=O) ₂ (C ₁ -C ₆ )alkyl, -P(=O)(OH) ₂ , -P(=O)(OH)(O(C ₁ -C ₆ )alkyl),-P(=O)(O(C ₁ -C ₆ )alkyl) ₂ , - P(=O)(OH)(O(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ -C ₁₀ )aryl) ₂ , -P(=O)(OH)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl) ₂ , - P(=O)(OH)(NH(C ₁ -C ₆ )alkyl),-P(=O)(NH(C ₁ -C ₆ )alkyl) ₂ , -P(=O)(OH)(NH(C ₆ -C ₁₀ )aryl), - P(=O)(O(C ₁ -C ₆ )alkyl)(NH(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₆ -C ₁₀ )aryl) ₂ , -P(=O)(OH)(NH(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ - C ₁₀ )aryl)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl) ₂ , - P(=O)(NH ₂ )(O(C ₁ -C ₆ )alkyl), -P(=O)(NH ₂ )(O(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl)(O(C ₆ - C ₁₀ )aryl), -P(=O)(NH ₂ )(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl)(O(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl), or -P(=O)(NH(C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl); represents a 4- to 10-membered saturated or partially saturated alkyl or heteroalkyl chain, optionally substituted with one or more Y; each Y is independently -OH, -O(C ₁ -C ₆ )alkyl, -SH, -S(C ₁ -C ₆ )alkyl, -NH ₂ , -NH(C ₁ - C ₆ )alkyl, -N((C ₁ -C ₆ )alkyl) ₂ , halo, -CN, -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ - C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, - (C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)(C ₁ - C ₆ )alkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)(C ₆ -C ₁₀ )aryl, - C(=O)(C ₁ -C ₆ )alkyl(C6-C10)aryl, -C(=O)(C ₅ -C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl(C5- C ₁₀ )heteroaryl, -C(=O)OH, -C(=O)O(C ₁ -C ₆ )alkyl, -C(=O)O(C ₁ -C ₆ )heteroalkyl, -C(=O)O(C ₃ - C ₇ )cycloalkyl, -C(=O)O(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)O(C ₅ -C ₁₀ )heteroaryl, -C(=O)O(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - C(=O)NH(C ₁ -C ₆ )alkyl, -C(=O)NH(C ₁ -C ₆ )heteroalkyl, -C(=O)NH(C ₃ -C ₇ )cycloalkyl, - C(=O)NH(C ₃ -C ₇ )heterocycloalkyl, -C(=O)NH(C ₆ -C ₁₀ )aryl, -C(=O)NH(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -C(=O)NH(C ₅ -C ₁₀ )heteroaryl, -C(=O)NH(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - S(=O) ₂ (C ₁ -C ₆ )alkyl, -P(=O)(OH) ₂ , -P(=O)(OH)(O(C ₁ -C ₆ )alkyl),-P(=O)(O(C ₁ -C ₆ )alkyl) ₂ , - P(=O)(OH)(O(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ -C ₁₀ )aryl) ₂ , -P(=O)(OH)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C6-C10)aryl)(O(C ₁ -C ₆ )alkyl(C6-C10)aryl), -P(=O)(O(C ₁ -C ₆ )alkyl(C6-C10)aryl)2, - P(=O)(OH)(NH(C ₁ -C ₆ )alkyl),-P(=O)(NH(C ₁ -C ₆ )alkyl) ₂ , -P(=O)(OH)(NH(C ₆ -C ₁₀ )aryl), - P(=O)(O(C ₁ -C ₆ )alkyl)(NH(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₆ -C ₁₀ )aryl) ₂ , -P(=O)(OH)(NH(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₁ -C ₆ )alkyl)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(O(C ₆ - C ₁₀ )aryl)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl) ₂ , - P(=O)(NH ₂ )(O(C ₁ -C ₆ )alkyl), -P(=O)(NH ₂ )(O(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl)(O(C ₆ - C ₁₀ )aryl), -P(=O)(NH ₂ )(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₁ -C ₆ )alkyl)(O(C ₁ - C ₆ )alkyl(C ₆ -C ₁₀ )aryl), -P(=O)(NH(C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl), or - P(=O)(NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl)(O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl); R ² is H or selected from the group consisting of -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ - C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, - (C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ -C ₆ )heteroalkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₁ - C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )heterocycloalkyl, -C(=O)(C ₆ -C ₁₀ )aryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)(C ₅ - C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl, - C(=O)CH(NH ₂ )(C ₃ -C ₇ )cycloalkyl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )cycloalkyl, - C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₃ -C ₇ )cycloalkyl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl)(C ₃ - C ₇ )cycloalkyl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )cycloalkyl, - C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )cycloalkyl, -C(=O)CH(NH ₂ )(C ₃ - C ₇ )heterocycloalkyl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(N((C ₁ - C ₆ )alkyl) ₂ )(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(N((C ₁ - C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)CH(NH ₂ )(C ₆ -C ₁₀ )aryl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₆ -C ₁₀ )aryl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₆ -C ₁₀ )aryl, - C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl(C ₆ - C ₁₀ )aryl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)CH(NH ₂ )(C ₅ - C ₁₀ )heteroaryl, -C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(N((C ₁ - C ₆ )alkyl) ₂ )(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(NH ₂ )(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, - C(=O)CH(NH(C ₁ -C ₆ )alkyl)(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)CH(N((C ₁ -C ₆ )alkyl) ₂ )(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ -C ₆ )alkyl, -C(=O)O-(C ₁ -C ₆ )heteroalkyl, -C(=O)O- (C ₁ -C ₆ )haloalkyl, -C(=O)O-(C ₃ -C ₇ )cycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, - C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O- (C ₆ -C ₁₀ )aryl, -C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)O-(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -C(=O)O-(C ₁ - C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )heteroalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, - C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ -C ₇ )cycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ - C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, - C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -C(=O)O-(C ₁ -C ₆ )alkyl- C(=O)O-(C ₆ -C ₁₀ )aryl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)O- (C ₁ -C ₆ )alkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, -C(=O)O-(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, wherein each instance of -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ - C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, - (C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl is optionally and independently substituted with one or more -OH, -NH ₂ , halo, -CN, -(C ₁ - C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, - (C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl-(C ₃ - C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, or -(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl; R ³ is H or selected from the group consisting of -C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ - C ₆ )heteroalkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ - C ₇ )heterocycloalkyl, -C(=O)(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -C(=O)(C ₆ -C ₁₀ )aryl, - C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -C(=O)(C ₅ -C ₁₀ )heteroaryl, -C(=O)(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, wherein each instance of -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ - C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, - (C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl is optionally and independently substituted with one or more -OH, -NH2, halo, -CN, -(C1- C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, - (C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, -(C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ - C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ - C ₁₀ )heteroaryl, or -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl; and R ⁴ is -OH, -O(C ₁ -C ₆ )alkyl, -O(C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -SH, -S(C ₁ -C ₆ )alkyl, -S(C ₆ -C ₁₀ )aryl, -S(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -NH ₂ , -NH(C ₁ -C ₆ )alkyl, -N((C ₁ -C ₆ )alkyl) ₂ , - NH(C ₆ -C ₁₀ )aryl, -NH(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -O(C ₂ -C ₆ )alkenyl, -O(C ₂ -C ₆ )heteroalkenyl, - O(C ₂ -C ₆ )haloalkenyl, -O(C ₂ -C ₆ )alkynyl, -O(C ₂ -C ₆ )heteroalkynyl, -O(C ₂ -C ₆ )haloalkynyl, - O(C ₁ -C ₆ )heteroalkyl, -O(C ₁ -C ₆ )haloalkyl, -O(C ₃ -C ₇ )cycloalkyl, -O(C ₃ -C ₇ )heterocycloalkyl, - O(C ₅ -C ₁₀ )heteroaryl, -O(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -NH(C ₂ -C ₆ )alkenyl, -NH(C ₂ - C ₆ )heteroalkenyl, -NH(C ₂ -C ₆ )haloalkenyl, -NH(C ₂ -C ₆ )alkynyl, -NH(C ₂ -C ₆ )heteroalkynyl, - NH(C ₂ -C ₆ )haloalkynyl, -NH(C ₁ -C ₆ )heteroalkyl, -NH(C ₁ -C ₆ )haloalkyl, -NH(C ₃ - C ₇ )cycloalkyl, -NH(C ₃ -C ₇ )heterocycloalkyl, -NH(C ₅ -C ₁₀ )heteroaryl, -NH(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )heteroalkyl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ -C ₇ )cycloalkyl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ - C ₇ )heterocycloalkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, -NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -NH(C ₁ -C ₆ )heteroalkyl- C(=O)O-(C ₁ -C ₆ )heteroalkyl, -NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, -NH(C ₁ - C ₆ )heteroalkyl-C(=O)O-(C ₃ -C ₇ )cycloalkyl, -NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, -NH(C ₁ - C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -NH(C ₁ -C ₆ )heteroalkyl- C(=O)O-(C ₆ -C ₁₀ )aryl, -NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -NH(C ₁ - C ₆ )heteroalkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, -NH(C ₁ -C ₆ )heteroalkyl-C(=O)O-(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl, -NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -NH(C ₁ - C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )heteroalkyl, -NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, - NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₃ -C ₇ )cycloalkyl, -NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ - C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₃ -C ₇ )heterocycloalkyl, -NH(C ₁ - C6)haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C3-C7)heterocycloalkyl, -NH(C ₁ -C ₆ )haloalkyl-C(=O)O- (C ₆ -C ₁₀ )aryl, -NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -NH(C ₁ -C ₆ )haloalkyl- C(=O)O-(C ₅ -C ₁₀ )heteroaryl, and -NH(C ₁ -C ₆ )haloalkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl, wherein each instance of -(C ₁ -C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ - C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, -(C ₂ -C ₆ )haloalkenyl, -(C ₂ -C ₆ )alkynyl, - (C ₂ -C ₆ )heteroalkynyl, -(C ₂ -C ₆ )haloalkynyl, -(C ₃ -C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, and -(C ₁ -C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl is optionally and independently substituted with one or more -OH, -NH ₂ , halo, -CN, -(C ₁ - C ₆ )alkyl, -(C ₁ -C ₆ )heteroalkyl, -(C ₁ -C ₆ )haloalkyl, -(C ₂ -C ₆ )alkenyl, -(C ₂ -C ₆ )heteroalkenyl, - (C2-C6)haloalkenyl, -(C2-C6)alkynyl, -(C2-C6)heteroalkynyl, -(C2-C6)haloalkynyl-(C3- C ₇ )cycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -(C ₃ -C ₇ )heterocycloalkyl, -(C ₁ -C ₆ )alkyl(C ₃ - C ₇ )heterocycloalkyl, -(C ₆ -C ₁₀ )aryl, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -(C ₅ -C ₁₀ )heteroaryl, or -(C ₁ - C ₆ )alkyl(C ₅ -C ₁₀ )heteroaryl; including enantiomers, racemic and scalemic mixtures, and pharmaceutically acceptable salts thereof. [0059] Embodiment 39. The compound of Embodiment 38, having Formula (VIII) wherein: X ¹ is O, CH ₂ , CH((C ₁ -C ₆ )alkyl), or CH(NH ₂ ); represents a 6- to 8-membered saturated or partially saturated alkyl or heteroalkyl chain, optionally substituted with one or more Y; L is -(C ₆ -C ₁₀ )aryl-O-, -(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl-O-, -(C ₅ -C ₁₀ )heteroaryl-O-, or -(C ₁ - C6)alkyl(C ₅ -C ₁₀ )heteroaryl-O-, each optionally and independently substituted with one or more L’; R ³ is H, -C(=O)(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ -C ₆ )heteroalkyl, -C(=O)(C ₃ -C ₇ )cycloalkyl, - C(=O)(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -C(=O)(C ₃ -C ₇ )heterocycloalkyl, -C(=O)(C ₁ - C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, -C(=O)(C ₆ -C ₁₀ )aryl, or -C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl; and R ⁴ is -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )heteroalkyl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )haloalkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ -C ₇ )cycloalkyl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )cycloalkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₃ - C ₇ )heterocycloalkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₃ -C ₇ )heterocycloalkyl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₅ -C ₁₀ )heteroaryl, or -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₅ - C ₁₀ )heteroaryl. [0060] Embodiment 40. The compound of Embodiment 39, having Formula (IX)

wherein: R ³ is H, -C(=O)(C ₁ -C ₆ )alkyl -C(=O)(C ₆ -C ₁₀ )aryl, or -C(=O)(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl; represents either a single or double bond; R ⁴ is -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl, -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₆ -C ₁₀ )aryl, or - NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl; L ¹ and L ² are both CH ₂ or S, and is a single bond; or L ¹ and L ² are both CH, and is a double bond; m is 0, 1, or 2; and n is 0, 1, or 2. [0061] Embodiment 41. The compound of Embodiment 40, wherein is a single bond. [0062] Embodiment 42. The compound of either Embodiment 40 or Embodiment 41, wherein L ¹ and L ² are both CH ₂ . [0063] Embodiment 43. The compound of any one of Embodiments 40-42, wherein m and n are 1. [0064] Embodiment 44. The compound of any one of Embodiments 38-43, wherein R ³ is H or C(=O)(C ₁ -C ₆ )alkyl. [0065] Embodiment 45. The compound of any one of Embodiments 38-44, wherein R ⁴ is -NH(C ₁ -C ₆ )alkyl-C(=O)O-(C ₁ -C ₆ )alkyl. [0066] Embodiment 46. The compound of Embodiment 40, wherein R ⁴ is -NHCH(Me)- C(=O)O-2-ethylbutyl. [0067] Embodiment 47. A compound having any one of the formulae selected from the group consisting of: ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-15-cyano-2,11- dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecin-13-y l)methyl 2-phenylacetate; ((12aR,13R,15R,15aR,Z)-15-(4-aminopyrrolo[2,1-f][1,2,4]triaz in-7-yl)-15-cyano-2,11-dioxo- 2,3,4,5,8,9,10,11,12a,13,15,15a-dodecahydrofuro[3,4-b][1,4]d ioxacyclotetradecin-13- yl)methyl 2-phenylacetate; (12aR,13R,15R,15aR)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazin- 7-yl)-15-(hydroxymethyl)- 2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecin e-13-carbonitrile; ((18aR,19R,21R,21aR)-21-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-21-cyano-2,17- dioxoicosahydrofuro[3,4-b][1,4]dioxacycloicosin-19-yl)methyl isobutyrate; ((18aR,19R,21R,21aR)-21-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-21-cyano-2,17- dioxoicosahydrofuro[3,4-b][1,4]dioxacycloicosin-19-yl)methyl 2-phenylacetate; ((18aR,19R,21R,21aR,Z)-21-(4-aminopyrrolo[2,1-f][1,2,4]triaz in-7-yl)-21-cyano-2,17-dioxo- 2,3,4,5,6,7,8,11,12,13,14,15,16,17,18a,19,21,21a-octadecahyd rofuro[3,4- b][1,4]dioxacycloicosin-19-yl)methyl 2-phenylacetate; ((3S,10S,12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4] triazin-7-yl)-15-cyano-3,10- dimethyl-2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclot etradecin-13-yl)methyl 2- phenylacetate; ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-15-cyano-2,11- dioxooctahydrofuro[3,4-m][1,3,10,12]tetraoxa[6,7]dithiacyclo tetradecin-13-yl)methyl 2- phenylacetate; 2-ethylbutyl ((((18aR,19R,21R,21aR)-21-(4-aminopyrrolo[2,1-f][1,2,4]triaz in-7-yl)-21-cyano- 2,17-dioxoicosahydrofuro[3,4-b][1,4]dioxacycloicosin-19- yl)methoxy)(phenoxy)phosphoryl)-L-alaninate; 2-ethylbutyl ((((12aR,13R,15R,15aR,Z)-15-(4-aminopyrrolo[2,1-f][1,2,4]tri azin-7-yl)-15- cyano-2,11-dioxo-2,3,4,5,8,9,10,11,12a,13,15,15a-dodecahydro furo[3,4- b][1,4]dioxacyclotetradecin-13-yl)methoxy)(phenoxy)phosphory l)-L-alaninate; 2-ethylbutyl ((((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triaz in-7-yl)-15-cyano- 2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecin -13- yl)methoxy)(phenoxy)phosphoryl)-L-alaninate; (18aR,19R,21R,21aR)-19-(4-aminopyrrolo[2,1-f][1,2,4]triazin- 7-yl)-21-(hydroxymethyl)- 2,17-dioxoicosahydrofuro[3,4-b][1,4]dioxacycloicosine-19-car bonitrile; ((3S,10S,12aR,13R,15R,15aR)-3,10-diamino-15-(4-aminopyrrolo[ 2,1-f][1,2,4]triazin-7-yl)- 15-cyano-2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclot etradecin-13-yl)methyl 2- phenylacetate; and ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-15-cyano-2,11- dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecin-13-y l)methyl L-valinate. [0068] Embodiment 48. The compound of Embodiment 47 having the formula: ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-15-cyano-2,11- dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecin-13-y l)methyl 2-phenylacetate. [0069] Embodiment 49. The sacchrinate salt of the compound of Embodiment 48. [0070] Embodiment 50. A pharmaceutical composition comprising the compound of any one of Embodiments 1-49, admixed with a pharmaceutically acceptable carrier, diluent, or excipient. [0071] Embodiment 51. The pharmaceutical composition of Embodiment 50, further comprising one or more therapeutic compounds or compositions. [0072] Embodiment 52. The pharmaceutical composition of Embodiment 51, wherein the one or more therapeutic compounds or compositions is a second antiviral compound or composition. [0073] Embodiment 53. The pharmaceutical composition of Embodiment 52, wherein the second antiviral compound or composition is a protease inhibitor including but not limited to paxlovid. [0074] Embodiment 54. The pharmaceutical composition of Embodiment 53, wherein the second antiviral compound or composition is an RdRp inhibitor. [0075] Embodiment 55. The pharmaceutical composition of Embodiment 54, wherein the second antiviral compound or composition is remdesivir or molnupiravir. [0076] Embodiment 56. A method of inhibiting an RNA-dependent RNA polymerase, comprising administering to a subject patient infected with a virus a therapeutically effective amount of the compound of any one of Embodiments 1-49 or the pharmaceutical compositions of Embodiments 50-55. [0077] Embodiment 57. The method of embodiment 56, wherein the virus is at least one virus selected from the group consisting of Ebola (Makona) virus, Ebola (Kikwit) virus, Bundibugyo virus, Sudan virus, Marburg virus, respiratory syncytial virus (RSV), Nipah virus, measles virus, parainfluenza virus, Middle Eastern Respiratory Syndrome (MERS) virus, South Asian Respiratory syndrome-Coronavirus (SARS-CoV), SARS-COV-2, hepatitis C virus (HCV), Dengue virus, Zika virus, West Nile virus, Lassa virus, and Junin virus. [0078] Embodiment 58. A method of preventing, ameliorating, or treating an RNA viral infection, comprising administering to a subject in need thereof a therapeutically effective amount of the compound of any one of Embodiments 1-49 or the pharmaceutical compositions of Embodiments 50-55. [0079] Embodiment 59. The method of Embodiment 58, wherein the RNA viral infection is caused by at least one virus selected from the group consisting of Ebola (Makona) virus, Ebola (Kikwit) virus, Bundibugyo virus, Sudan virus, Marburg virus, respiratory syncytial virus (RSV), Nipah virus, measles virus, parainfluenza virus, Middle Eastern Respiratory Syndrome (MERS) virus, South Asian Respiratory syndrome-Coronavirus (SARS-CoV), SARS-COV-2, hepatitis C virus (HCV), Dengue virus, Zika virus, West Nile virus, Lassa virus, and Junin virus. [0080] Embodiment 60. The method of Embodiment 59, wherein the RNA viral infection is caused by SARS-COV-2. [0081] Embodiment 61. Any compound, composition, or method as described herein. Definitions [0082] The phrase “a” or “an” entity as used herein refers to one or more of that entity; for example, a compound refers to one or more compounds or at least one compound. As such, the terms “a” (or “an”), “one or more”, and “at least one” can be used interchangeably herein. [0083] The phrase "as defined herein above" refers to the broadest definition for each group as provided in the Summary of the Invention, the Detailed Description of the Invention, the Experimentals, or the broadest claim. In all other embodiments provided below, substituents which can be present in each embodiment and which are not explicitly defined retain the broadest definition provided in the Summary of the Invention. [0084] As used in this specification, whether in a transitional phrase or in the body of the claim, the terms "comprise(s)" and "comprising" are to be interpreted as having an open- ended meaning. That is, the terms are to be interpreted synonymously with the phrases "having at least" or "including at least". When used in the context of a process, the term "comprising" means that the process includes at least the recited steps, but may include additional steps. When used in the context of a compound or composition, the term "comprising" means that the compound or composition includes at least the recited features or components, but may also include additional features or components. [0085] As used herein, unless specifically indicated otherwise, the word "or" is used in the "inclusive" sense of "and/or" and not the "exclusive" sense of "either/or". [0086] The term "independently" is used herein to indicate that a variable is applied in any one instance without regard to the presence or absence of a variable having that same or a different definition within the same compound. Thus, in a compound in which “R” appears twice and is defined as "independently selected from” means that each instance of that R group is separately identified as one member of the set which follows in the definition of that R group. For example, “each R ¹ and R ² is independently selected from carbon and nitrogen" means that both R ¹ and R ² can be carbon, both R ¹ and R ² can be nitrogen, or R ¹ or R ² can be carbon and the other nitrogen or vice versa. [0087] When any variable occurs more than one time in any moiety or formula depicting and describing compounds employed or claimed in the present invention, its definition on each occurrence is independent of its definition at every other occurrence. Also, combinations of substituents and/or variables are permissible only if such compounds result in stable compounds. [0088] The symbols "*" at the end of a bond or a line drawn through a bond or “~~~~” drawn through a bond each refer to the point of attachment of a functional group or other chemical moiety to the rest of the molecule of which it is a part. [0089] A bond drawn into ring system (as opposed to connected at a distinct vertex) indicates that the bond may be attached to any of the suitable ring atoms. [0090] The term “optional” or “optionally” as used herein means that a subsequently described event or circumstance may, but need not, occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, “optionally substituted” means that the “optionally substituted” moiety may incorporate a hydrogen or a substituent. [0091] The phrase “optional bond” means that the bond may or may not be present, and that the description includes single, double, or triple bonds. If a substituent is designated to be a "bond" or "absent", the atoms linked to the substituents are then directly connected. [0092] The term "about" is used herein to mean approximately, in the region of, roughly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" is used herein to modify a numerical value above and below the stated value by a variance of 20%. [0093] Certain compounds disclosed herein may exhibit tautomerism. Tautomeric compounds can exist as two or more interconvertable species. Prototropic tautomers result from the migration of a covalently bonded hydrogen atom between two atoms. Tautomers generally exist in equilibrium and attempts to isolate an individual tautomers usually produce a mixture whose chemical and physical properties are consistent with a mixture of compounds. The position of the equilibrium is dependent on chemical features within the molecule. For example, in many aliphatic aldehydes and ketones, such as acetaldehyde, the keto form predominates while; in phenols, the enol form predominates. Common prototropic tautomers include keto/enol (-C(=O)-CH- -C(-OH)=CH-), amide/imidic acid (-C(=O)-NH- -C(-OH)=N-) and amidine (-C(=NR)-NH- -C(-NHR)=N-) tautomers. The latter two are particularly common in heteroaryl and heterocyclic rings and the present invention encompasses all tautomeric forms of the compounds. [0094] Technical and scientific terms used herein have the meaning commonly understood by one of skill in the art to which the present invention pertains, unless otherwise defined. Reference is made herein to various methodologies and materials known to those of skill in the art. Standard reference works setting forth the general principles of pharmacology include Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10 ^th Ed., McGraw Hill Companies Inc., New York (2001). Any suitable materials and/or methods known to those of skill can be utilized in carrying out the present invention. However, preferred materials and methods are described. Materials, reagents and the like to which reference are made in the following description and examples are obtainable from commercial sources, unless otherwise noted. [0095] The definitions described herein may be appended to form chemically-relevant combinations, such as “heteroalkylaryl,” “haloalkylheteroaryl,” “arylalkylheterocyclyl,” “alkylcarbonyl,” “alkoxyalkyl,” and the like. When the term “alkyl” is used as a suffix following another term, as in “phenylalkyl,” or “hydroxyalkyl,” this is intended to refer to an alkyl group, as defined above, being substituted with one to two substituents selected from the other specifically-named group. Thus, for example, “phenylalkyl” refers to an alkyl group having one to two phenyl substituents, and thus includes benzyl, phenylethyl, and biphenyl. An “alkylaminoalkyl” is an alkyl group having one to two alkylamino substituents. “Hydroxyalkyl" includes 2-hydroxyethyl, 2-hydroxypropyl, 1-(hydroxymethyl)-2- methylpropyl, 2-hydroxybutyl, 2,3-dihydroxybutyl, 2-(hydroxymethyl), 3-hydroxypropyl, and so forth. Accordingly, as used herein, the term “hydroxyalkyl” is used to define a subset of heteroalkyl groups defined below. The term -(ar)alkyl refers to either an unsubstituted alkyl or an aralkyl group. The term (hetero)aryl or (het)aryl refers to either an aryl or a heteroaryl group. [0096] The term “acyl” as used herein denotes a group of formula -C(=O)R wherein R is hydrogen or lower alkyl as defined herein. The term or "alkylcarbonyl" as used herein denotes a group of formula C(=O)R wherein R is alkyl as defined herein. The term C _1-6 acyl refers to a group -C(=O)R contain 6 carbon atoms. The term "arylcarbonyl" as used herein means a group of formula C(=O)R wherein R is an aryl group; the term "benzoyl" as used herein an "arylcarbonyl" group wherein R is phenyl. [0097] The term “alkyl” as used herein denotes an unbranched or branched chain, saturated, monovalent hydrocarbon residue containing 1 to 12 carbon atoms. The term “lower alkyl” or “C ₁ -C ₆ alkyl” as used herein denotes a straight or branched chain hydrocarbon residue containing 1 to 6 carbon atoms. "C ₁ - ₁₂ alkyl" as used herein refers to an alkyl composed of 1 to 12 carbons. Examples of alkyl groups include, but are not limited to, lower alkyl groups include methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, t-butyl or pentyl, isopentyl, neopentyl, hexyl, heptyl, and octyl. [0098] When the term “alkyl” is used as a suffix following another term, as in “phenylalkyl,” or “hydroxyalkyl,” this is intended to refer to an alkyl group, as defined above, being substituted with one to two substituents selected from the other specifically- named group. Thus, for example, “phenylalkyl” denotes the radical R'R"-, wherein R' is a phenyl radical, and R" is an alkylene radical as defined herein with the understanding that the attachment point of the phenylalkyl moiety will be on the alkylene radical. Examples of arylalkyl radicals include, but are not limited to, benzyl, phenylethyl, 3-phenylpropyl. The terms “arylalkyl” or "aralkyl" are interpreted similarly except R' is an aryl radical. The terms "(het)arylalkyl" or "(het)aralkyl" are interpreted similarly except R' is optionally an aryl or a heteroaryl radical. [0099] When a range of values is listed, it is intended to encompass each value and sub– range within the range. For example, “C _1–6 alkyl” is intended to encompass, C ₁ , C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C _1–6 , C _1–5 , C _1–4 , C _1–3 , C _1–2 , C _2–6 , C _2–5 , C _2–4 , C _2–3 , C _3–6 , C _3–5 , C _3–4 , C _4–6 , C _4–5 , and C _5–6 alkyl. [00100] “Alkyl” refers to a radical of a straight–chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms (“C _1–20 alkyl”). In some embodiments, an alkyl group has 1 to 15 carbon atoms (“C _1–15 alkyl”). In some embodiments, an alkyl group has 1 to 14 carbon atoms (“C _1–14 alkyl”). In some embodiments, an alkyl group has 1 to 13 carbon atoms (“C _1–13 alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C _1–12 alkyl”). In some embodiments, an alkyl group has 1 to 11 carbon atoms (“C _1–11 alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C _1–10 alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C _1–9 alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C _1–8 alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C _1–7 alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C _1–6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C _1–5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C _1–4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C _1–3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C _1–2 alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C ₁ alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C _2–6 alkyl”). Examples of C _1–6 alkyl groups include methyl (C ₁ ), ethyl (C ₂ ), n–propyl (C ₃ ), isopropyl (C ₃ ), n–butyl (C ₄ ), tert–butyl (C ₄ ), sec–butyl (C ₄ ), iso–butyl (C ₄ ), n– pentyl (C ₅ ), 3–pentanyl (C ₅ ), amyl (C ₅ ), neopentyl (C ₅ ), 3–methyl–2–butanyl (C ₅ ), tertiary amyl (C ₅ ), and n–hexyl (C ₆ ). Additional examples of alkyl groups include n–heptyl (C ₇ ), n– octyl (C ₈ ) and the like. [00101] “Alkenyl” or “olefin” refers to a radical of a straight–chain or branched hydrocarbon group having from 2 to 10 carbon atoms and 1, 2, 3, or 4 carbon-carbon double bonds (“C _2–10 alkenyl”). In some embodiments, an alkenyl group has 2 to 9 carbon atoms (“C _2–9 alkenyl”). In some embodiments, an alkenyl group has 2 to 8 carbon atoms (“C _2–8 alkenyl”). In some embodiments, an alkenyl group has 2 to 7 carbon atoms (“C _2–7 alkenyl”). In some embodiments, an alkenyl group has 2 to 6 carbon atoms (“C _2–6 alkenyl”). In some embodiments, an alkenyl group has 2 to 5 carbon atoms (“C _2–5 alkenyl”). In some embodiments, an alkenyl group has 2 to 4 carbon atoms (“C _2–4 alkenyl”). In some embodiments, an alkenyl group has 2 to 3 carbon atoms (“C _2–3 alkenyl”). In some embodiments, an alkenyl group has 2 carbon atoms (“C ₂ alkenyl”). The one or more carbon– carbon double bonds can be internal (such as in 2–butenyl) or terminal (such as in 1–butenyl). Examples of C _2–4 alkenyl groups include ethenyl (C ₂ ), 1–propenyl (C ₃ ), 2–propenyl (C ₃ ), 1– butenyl (C ₄ ), 2–butenyl (C ₄ ), butadienyl (C ₄ ), and the like. Examples of C _2–6 alkenyl groups include the aforementioned C _2–4 alkenyl groups as well as pentenyl (C ₅ ), pentadienyl (C ₅ ), hexenyl (C ₆ ), and the like. Additional examples of alkenyl include heptenyl (C ₇ ), octenyl (C ₈ ), octatrienyl (C ₈ ), and the like. [00102] “Alkynyl” refers to a radical of a straight–chain or branched hydrocarbon group having from 2 to 10 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C _2–10 alkynyl”). In some embodiments, an alkynyl group has 2 to 9 carbon atoms (“C _2–9 alkynyl”). In some embodiments, an alkynyl group has 2 to 8 carbon atoms (“C _2–8 alkynyl”). In some embodiments, an alkynyl group has 2 to 7 carbon atoms (“C _2–7 alkynyl”). In some embodiments, an alkynyl group has 2 to 6 carbon atoms (“C _2–6 alkynyl”). In some embodiments, an alkynyl group has 2 to 5 carbon atoms (“C _2–5 alkynyl”). In some embodiments, an alkynyl group has 2 to 4 carbon atoms (“C _2–4 alkynyl”). In some embodiments, an alkynyl group has 2 to 3 carbon atoms (“C _2–3 alkynyl”). In some embodiments, an alkynyl group has 2 carbon atoms (“C ₂ alkynyl”). The one or more carbon– carbon triple bonds can be internal (such as in 2–butynyl) or terminal (such as in 1–butynyl). Examples of C _2–4 alkynyl groups include, without limitation, ethynyl (C ₂ ), 1–propynyl (C ₃ ), 2–propynyl (C ₃ ), 1–butynyl (C ₄ ), 2–butynyl (C ₄ ), and the like. Examples of C _2–6 alkenyl groups include the aforementioned C _2–4 alkynyl groups as well as pentynyl (C ₅ ), hexynyl (C ₆ ), and the like. Additional examples of alkynyl include heptynyl (C ₇ ), octynyl (C ₈ ), and the like. [00103] The terms “haloalkyl” or “halo-lower alkyl” or “lower haloalkyl” refers to a straight or branched chain hydrocarbon residue containing 1 to 6 carbon atoms wherein one or more carbon atoms are substituted with one or more halogen atoms. [00104] The term "alkylene" or "alkylenyl" as used herein denotes a divalent saturated linear hydrocarbon radical of 1 to 10 carbon atoms (e.g., (CH ₂ ) _n )or a branched saturated divalent hydrocarbon radical of 2 to 10 carbon atoms (e.g., -CHMe- or -CH ₂ CH(i-Pr)CH ₂ -), unless otherwise indicated. Except in the case of methylene, the open valences of an alkylene group are not attached to the same atom. Examples of alkylene radicals include, but are not limited to, methylene, ethylene, propylene, 2-methyl-propylene, 1,1-dimethyl-ethylene, butylene, 2-ethylbutylene. [00105] The term "alkoxy" as used herein means an -O-alkyl group, wherein alkyl is as defined above such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, i-butyloxy, t- butyloxy, pentyloxy, hexyloxy, including their isomers. "Lower alkoxy" as used herein denotes an alkoxy group with a "lower alkyl" group as previously defined. "C ₁ - ₁₀ alkoxy" as used herein refers to an-O-alkyl wherein alkyl is C _1-10 . [00106] The term "hydroxyalkyl" as used herein denotes an alkyl radical as herein defined wherein one to three hydrogen atoms on different carbon atoms is/are replaced by hydroxyl groups. [00107] The terms "alkylsulfonyl" and "arylsulfonyl" as used herein refers to a group of formula -S(=O) ₂ R wherein R is alkyl or aryl respectively and alkyl and aryl are as defined herein. The term “heteroalkylsulfonyl” as used herein refers herein denotes a group of formula -S(=O) ₂ R wherein R is “heteroalkyl. [00108] The term “heteroalkyl” as used herein is an alkyl group where one or more carbon atoms is replaced by a nitrogen, oxygen, sulfur or phosphorus atom and the valency is adjusted according to the heteroatom replacement either by addition or removal of -H, =O, or alkyl moieties, optionally substituted with one or more halogen or hydroxy moieties. “hetero (C ₁ -C ₆ )alkyl” as used herein refers to a heteroalkyl group wherein the carbon chain is 1-6 carbon atoms, branched or unbranched, optionally substituted with one or more halogen or hydroxy moieties. [00109] The terms "alkylsulfonylamino" and "arylsulfonylamino"as used herein refers to a group of formula -NR'S(=O) ₂ R wherein R is alkyl or aryl respectively, R' is hydrogen or C _{1- 3} alkyl, and alkyl and aryl are as defined herein. [00110] The term “cycloalkyl” as used herein refers to a saturated carbocyclic ring containing 3 to 8 carbon atoms, i.e. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. "C _3-7 cycloalkyl" as used herein refers to an cycloalkyl composed of 3 to 7 carbons in the carbocyclic ring. [00111] The term carboxy-alkyl as used herein refers to an alkyl moiety wherein one, hydrogen atom has been replaced with a carboxyl with the understanding that the point of attachment of the heteroalkyl radical is through a carbon atom. The term “carboxy” or “carboxyl” refers to a –CO ₂ H moiety. [00112] The term "heteroaryl” or "heteroaromatic" as used herein means a monocyclic or bicyclic radical of 5 to 12 ring atoms having at least one aromatic ring containing four to eight atoms per ring, incorporating one or more N, O, or S heteroatoms, the remaining ring atoms being carbon, with the understanding that the attachment point of the heteroaryl radical will be on an aromatic ring. As well known to those skilled in the art, heteroaryl rings have less aromatic character than their all-carbon counter parts. Thus, for the purposes of the invention, a heteroaryl group need only have some degree of aromatic character. Examples of heteroaryl moieties include monocyclic aromatic heterocycles having 5 to 6 ring atoms and 1 to 3 heteroatoms include, but is not limited to, pyridinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, oxazol, isoxazole, thiazole, isothiazole, triazoline, thiadiazole and oxadiaxoline which can optionally be substituted with one or more, preferably one or two substituents selected from hydroxy, cyano, alkyl, alkoxy, thio, lower haloalkoxy, alkylthio, halo, lower haloalkyl, alkylsulfinyl, alkylsulfonyl, halogen, amino, alkylamino,dialkylamino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl, nitro, alkoxycarbonyl and carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, arylcarbamoyl, alkylcarbonylamino and arylcarbonylamino. Examples of bicyclic moieties include, but are not limited to, quinolinyl, isoquinolinyl, benzofuryl, benzothiophenyl, benzoxazole, benzisoxazole, benzothiazole and benzisothiazole. Bicyclic moieties can be optionally substituted on either ring; however the point of attachment is on a ring containing a heteroatom. [00113] The term "heterocyclyl", “heterocycloalkyl” or "heterocycle" as used herein denotes a monovalent saturated cyclic radical, consisting of one or more rings, preferably one to two rings, including spirocyclic ring systems, of three to eight atoms per ring, incorporating one or more ring heteroatoms (chosen from N,O or S(O) _0-2 ), and which can optionally be independently substituted with one or more, preferably one or two substituents selected from hydroxy, oxo, cyano, lower alkyl, lower alkoxy, lower haloalkoxy, alkylthio, halo, lower haloalkyl, hydroxyalkyl, nitro, alkoxycarbonyl, amino, alkylamino, alkylsulfonyl, arylsulfonyl, alkylaminosulfonyl, arylaminosulfonyl, alkylsulfonylamino, arylsulfonylamino, alkylaminocarbonyl, arylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, unless otherwise indicated. Examples of heterocyclic radicals include, but are not limited to, azetidinyl, pyrrolidinyl, hexahydroazepinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl, oxazolidinyl, thiazolidinyl, isoxazolidinyl, morpholinyl, piperazinyl, piperidinyl, tetrahydropyranyl, thiomorpholinyl, quinuclidinyl and imidazolinyl. [00114] “Heterocyclyl” or “heterocyclic” refers to a group or radical of a 3– to 14– membered non–aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“3–14 membered heterocyclyl”). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or polycyclic (e.g., a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”) or tricyclic system (“tricyclic heterocyclyl”)), and can be saturated or can contain one or more carbon– carbon double or triple bonds. Heterocyclyl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. [00115] In some embodiments, a heterocyclyl group is a 5–10 membered non–aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–10 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–8 membered non–aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–6 membered non–aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heterocyclyl”). In some embodiments, the 5–6 membered heterocyclyl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. [00116] Exemplary 3–membered heterocyclyl groups containing 1 heteroatom include, without limitation, azirdinyl, oxiranyl, and thiiranyl. Exemplary 4–membered heterocyclyl groups containing 1 heteroatom include, without limitation, azetidinyl, oxetanyl and thietanyl. Exemplary 5–membered heterocyclyl groups containing 1 heteroatom include, without limitation, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl–2,5–dione. Exemplary 5– membered heterocyclyl groups containing 2 heteroatoms include, without limitation, dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5–membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6–membered heterocyclyl groups containing 1 heteroatom include, without limitation, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6–membered heterocyclyl groups containing 2 heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6–membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazinanyl. Exemplary 7–membered heterocyclyl groups containing 1 heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl. Exemplary 8–membered heterocyclyl groups containing 1 heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro–1,8–naphthyridinyl, octahydropyrrolo[3,2–b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H–benzo[e][1,4]diazepinyl, 1,4,5,7–tetrahydropyrano[3,4–b]pyrrolyl, 5,6–dihydro–4H–furo[3,2–b]pyrrolyl, 6,7–dihydro– 5H–furo[3,2–b]pyranyl, 5,7–dihydro–4H–thieno[2,3–c]pyranyl, 2,3–dihydro–1H– pyrrolo[2,3–b]pyridinyl, 2,3–dihydrofuro[2,3–b]pyridinyl, 4,5,6,7–tetrahydro–1H–pyrrolo- [2,3–b]pyridinyl, 4,5,6,7–tetrahydrofuro[3,2–c]pyridinyl, 4,5,6,7–tetrahydrothieno[3,2– b]pyridinyl, 1,2,3,4–tetrahydro–1,6–naphthyridinyl, and the like. [00117] “Aryl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 pi electrons shared in a cyclic array) having 6–14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system (“C _6–14 aryl”). In some embodiments, an aryl group has 6 ring carbon atoms (“C ₆ aryl”; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms (“C ₁₀ aryl”; e.g., naphthyl such as 1–naphthyl (α-naphthyl) and 2–naphthyl (β-naphthyl)). In some embodiments, an aryl group has 14 ring carbon atoms (“C ₁₄ aryl”; e.g., anthracyl). “Aryl” also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. [00118] “Heteroaryl” refers to a radical of a 5–14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 pi electrons shared in a cyclic array) having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–14 membered heteroaryl”). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heteroaryl” includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl/heteroaryl) ring system. Polycyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2–indolyl) or the ring that does not contain a heteroatom (e.g., 5–indolyl). [00119] In some embodiments, a heteroaryl group is a 5–10 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–10 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5–8 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5–6 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heteroaryl”). In some embodiments, the 5–6 membered heteroaryl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heteroaryl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. [00120] Exemplary 5–membered heteroaryl groups containing 1 heteroatom include, without limitation, pyrrolyl, furanyl and thiophenyl. Exemplary 5–membered heteroaryl groups containing 2 heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5–membered heteroaryl groups containing 3 heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5–membered heteroaryl groups containing 4 heteroatoms include, without limitation, tetrazolyl. Exemplary 6–membered heteroaryl groups containing 1 heteroatom include, without limitation, pyridinyl. Exemplary 6–membered heteroaryl groups containing 2 heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6–membered heteroaryl groups containing 3 or 4 heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively. Exemplary 7–membered heteroaryl groups containing 1 heteroatom include, without limitation, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6– bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6–bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Exemplary tricyclic heteroaryl groups include, without limitation, phenanthridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl and phenazinyl. [00121] “Saturated” refers to a ring moiety that does not contain a double or triple bond, i.e., the ring contains all single bonds. [00122] Alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may be optionally substituted. Optionally substituted refers to a group which may be substituted or unsubstituted. In general, the term “substituted” means that at least one hydrogen present on a group is replaced with a non-hydrogen substituent, and which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Heteroatoms such as nitrogen, oxygen, and sulfur may have hydrogen substituents and/or non-hydrogen substituents which satisfy the valencies of the heteroatoms and results in the formation of a stable compound. [00123] Exemplary non-hydrogen substituents wherein a moiety is “optionally substituted” as used herein means the moiety may be substituted with any additional moiety selected from, but not limited to, the group consisting of halogen, –CN, –NO ₂ , –N ₃ , –SO ₂ H, – SO ₃ H, –OH, –OR ^aa , –N(R ^bb ) ₂ , –N(OR ^cc )R ^bb , –SH, –SR ^aa , –C(=O)R ^aa , –CO ₂ H, –CHO, – CO ₂ R ^aa , –OC(=O)R ^aa , –OCO ₂ R ^aa , –C(=O)N(R ^bb ) ₂ , –OC(=O)N(R ^bb ) ₂ , –NR ^bb C(=O)R ^aa , – NR ^bb CO ₂ R ^aa , –NR ^bb C(=O)N(R ^bb ) ₂ , –C(=NR ^bb )R ^aa , –C(=NR ^bb )OR ^aa , –OC(=NR ^bb )R ^aa , – OC(=NR ^bb )OR ^aa , –C(=NR ^bb )N(R ^bb ) ₂ , –OC(=NR ^bb )N(R ^bb ) ₂ , –NR ^bb C(=NR ^bb )N(R ^bb ) ₂ , – C(=O)NR ^bb SO ₂ R ^aa , –NR ^bb SO ₂ R ^aa , –SO ₂ N(R ^bb ) ₂ , –SO ₂ R ^aa , –S(=O)R ^aa , –OS(=O)R ^aa , - B(OR ^cc ) ₂ , C _1–10 alkyl, C _2–10 alkenyl, C _2–10 alkynyl, C _3–14 carbocyclyl, 3– to 14- membered heterocyclyl, C _6–14 aryl, and 5– to 14- membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups, or two geminal hydrogens on a carbon atom are replaced with the group =O; each instance of R ^aa is, independently, selected from the group consisting of C _1–10 alkyl, C _1–10 perhaloalkyl, C _2–10 alkenyl, C _2–10 alkynyl, C _3–14 carbocyclyl, 3– to 14- membered heterocyclyl, C _6–14 aryl, and 5– to 14- membered heteroaryl, or two R ^aa groups are joined to form a 3– to 14- membered heterocyclyl or 5– to 14- membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^bb is, independently, selected from the group consisting of hydrogen, –OH, –OR ^aa , –N(R ^cc ) ₂ , –CN, –C(=O)R ^aa , – C(=O)N(R ^cc ) ₂ , –CO ₂ R ^aa , –SO ₂ R ^aa , –SO ₂ N(R ^cc ) ₂ , –SOR ^aa , C _1–10 alkyl, C _1–10 perhaloalkyl, C _2–10 alkenyl, C _2–10 alkynyl, C _3–14 carbocyclyl, 3– to 14- membered heterocyclyl, C _6–14 aryl, and 5– to 14- membered heteroaryl, or two R ^bb groups are joined to form a 3– to 14- membered heterocyclyl or 5– to 14- membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^cc is, independently, selected from the group consisting of hydrogen, C _1–10 alkyl, C _1–10 perhaloalkyl, C _2–10 alkenyl, C _2–10 alkynyl, C _3–14 carbocyclyl, 3– to 14- membered heterocyclyl, C _6–14 aryl, and 5– to 14- membered heteroaryl, or two R ^cc groups are joined to form a 3– to 14- membered heterocyclyl or 5– to 14- membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; and each instance of R ^dd is, independently, selected from the group consisting of halogen, –CN, –NO ₂ , –N ₃ , – SO ₂ H, –SO ₃ H, –OH, –OC _1–6 alkyl, –ON(C _1–6 alkyl) ₂ , –N(C _1–6 alkyl) ₂ , –N(OC _1–6 alkyl)(C _1–6 alkyl), –N(OH)(C _1–6 alkyl), –NH(OH), –SH, –SC _1–6 alkyl, –C(=O)(C _1–6 alkyl), –CO ₂ H, – CO ₂ (C _1–6 alkyl), –OC(=O)(C _1–6 alkyl), –OCO ₂ (C _1–6 alkyl), –C(=O)NH ₂ , –C(=O)N(C _1–6 alkyl) ₂ , –OC(=O)NH(C _1–6 alkyl), –NHC(=O)( C _1–6 alkyl), –N(C _1–6 alkyl)C(=O)( C _1–6 alkyl), –NHCO ₂ (C _1–6 alkyl), –NHC(=O)N(C _1–6 alkyl) ₂ , –NHC(=O)NH(C _1–6 alkyl), –NHC(=O)NH ₂ , –C(=NH)O(C _1–6 alkyl),–OC(=NH)(C _1–6 alkyl), –OC(=NH)OC _1–6 alkyl, –C(=NH)N(C _1–6 alkyl) ₂ , –C(=NH)NH(C _1–6 alkyl), –C(=NH)NH ₂ , –OC(=NH)N(C _1–6 alkyl) ₂ , – OC(NH)NH(C _1–6 alkyl), –OC(NH)NH ₂ , –NHC(NH)N(C _1–6 alkyl) ₂ , –NHC(=NH)NH ₂ , – NHSO ₂ (C _1–6 alkyl), –SO ₂ N(C _1–6 alkyl) ₂ , –SO ₂ NH(C _1–6 alkyl), –SO ₂ NH ₂ ,–SO ₂ C _1–6 alkyl, - B(OH) ₂ , -B(OC _1–6 alkyl) ₂ ,C _1–6 alkyl, C _1–6 perhaloalkyl, C _2–6 alkenyl, C _2–6 alkynyl, C _3–10 carbocyclyl, C _6–10 aryl, 3–to 10- membered heterocyclyl, and 5- to 10- membered heteroaryl; or two geminal R ^dd substituents on a carbon atom may be joined to form =O. [00124] “Halo” or “halogen” refers to fluorine (fluoro, –F), chlorine (chloro, –Cl), bromine (bromo, –Br), or iodine (iodo, –I). [00125] As used herein, the term “composition” is intended to encompass a product comprising the specified ingredients, as well as any product which results, directly or indirectly, from combination of the specified ingredients. [00126] “Salt” includes any and all salts. “Pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al., describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66:1–19. Pharmaceutically acceptable salts include those derived from inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2–hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2– naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p–toluenesulfonate, undecanoate, valerate salts, and the like. Pharmaceutically acceptable salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N ⁺ (C _1–4 alkyl) ₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. [00127] Unless otherwise indicated, compounds described herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC). Compounds described herein can be in the form of individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. [00128] Unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, replacement of ¹⁹ F with ¹⁸ F, replacement of a carbon by a ¹³ C- or ¹⁴ C- enriched carbon, and/or replacement of an oxygen atom with ¹⁸ O, are within the scope of the disclosure. Other examples of isotopes include ¹⁵ N, ¹⁸ O, ¹⁷ O, ³¹ P, ³² P, ³⁵ S, ¹⁸ F, ³⁶ Cl and ¹²³ I. Compounds with such isotopically enriched atoms are useful, for example, as analytical tools or probes in biological assays. [00129] Certain isotopically-labelled compounds (e.g., those labeled with ³ H and ¹⁴ C) are useful in compound and/or substrate tissue distribution assays. Tritiated (i.e., ³ H) and carbon-14 (i.e., ¹⁴ C) isotopes are particularly preferred for their ease of preparation and detectability. [00130] Certain isotopically-labelled compounds of Formula (I) can be useful for medical imaging purposes, for example, those labeled with positron-emitting isotopes like ¹¹ C or ¹⁸ F can be useful for application in Positron Emission Tomography (PET) and those labeled with gamma ray emitting isotopes like ¹²³ I can be useful for application in Single Photon Emission Computed Tomography (SPECT). Further, substitution with heavier isotopes such as deuterium (i.e., ² H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances. Further, substitution with heavier isotopes such as deuterium (i.e., ² H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements), and hence, may be preferred in some circumstances. Additionally, isotopic substitution at a site where epimerization occurs may slow or reduce the epimerization process and thereby retain the more active or efficacious form of the compound for a longer period of time. Isotopically labeled compounds of Formula (I), in particular those containing isotopes with longer half- lives (t _1/2 >1 day), can generally be prepared by following procedures analogous to those disclosed in the Schemes and/or in the Examples herein below, by substituting an appropriate isotopically labeled reagent for a non-isotopically labeled reagent. [00131] If there is a discrepancy between a depicted structure and a name given to that structure, then the depicted structure controls. Additionally, if the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing all stereoisomers of it. In some cases, however, where more than one chiral center exists, the structures and names may be represented as single enantiomers to help describe the relative stereochemistry. Those skilled in the art of organic synthesis will know if the compounds are prepared as single enantiomers from the methods used to prepare them. [00132] The compounds described herein can also be used in combination with one or more additional therapeutic and/or prophylactic agents. As such, also provided herein are methods of treatment or prevention of the various viral infections provided herein, wherein the methods comprise administering to a subject in need thereof a compound of the disclosure and a therapeutically effective amount of one or more additional therapeutic and/or prophylactic agents (“therapeutic agent” is interchangeable with “prophylactic agent” as used herein). Accordingly, the compounds of the present invention and the additional therapeutic agents can be utilized for pre-exposure and post-exposure prophylaxis. [00133] In some embodiments, the additional therapeutic agent is an antiviral agent such as remdesivir (RDV, GS-5374), a nucleotide analog prodrug and an RNA-dependent RNA polymerase (RdRp) inhibitor. In some embodiments, the additional therapeutic agent is an antiviral agent such as molnupiravir. [00134] Any suitable antiviral agent can be used in the methods described herein. In some embodiments, the antiviral agent is selected from the group consisting of 5-substituted 2' - deoxyuridine analogues, nucleoside analogues, pyrophosphate analogues, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, entry inhibitors, acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, HCV NS5A inhibitors, NS5B inhibitors, influenza virus inhibitors, interferons, immunostimulators, oligonucleotides, antimitotic inhibitors, and combinations thereof. [00135] In some embodiments, the additional therapeutic agent is a 5-substituted 2' - deoxyuridine analogue. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of idoxuridine, trifluridine, brivudine (bromo vinyl deoxyuridine or “BVDU”), and combinations thereof. [00136] In some embodiments, the additional therapeutic agent is a nucleoside analogue. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of vidarabine, entecavir (ETV), telbivudine, lamivudine, adefovir dipivoxil, tenofovirdisoproxil fumarate (TDF) and combinations thereof. In some embodiments, the additional therapeutic agent is favipiravir, ribavirin, galidesivir, or a combination thereof. In some embodiments, the additional therapeutic agent is ~-D-N4-hydroxycytidine. [00137] In some embodiments, the additional therapeutic agent is a pyrophosphate analogue. For example, in some embodiments, the additional therapeutic agent is foscarnet or phosphonoacetic acid. In some embodiments, the additional therapeutic agent is foscarnet. [00138] In some embodiments, the additional therapeutic agent is nucleoside reverse transcriptase inhibitor. In some embodiments, the antiviral agent is zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, and combinations thereof. In some embodiments, the additional therapeutic agent is sangivamycin, β-d-N4- Hydroxycytidine (NHC), EIDD-2801, EIDD-1931, or a combination thereof. In some embodiments, the antiviral agent is MK-4482 (EIDD-2801). [00139] In some embodiments, the additional therapeutic agent is a non-nucleoside reverse transcriptase inhibitor. In some embodiments, the antiviral agent is selected from the group consisting of nevirapine, delavirdine, efavirenz, etravirine, rilpivirine, and combinations thereof. [00140] In some embodiments, the additional therapeutic agent is a protease inhibitor. In some embodiments, the protease inhibitor is a HIV protease inhibitor. For example, in some embodiments, the antiviral agent is selected from the group consisting of saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, darunavir, tipranavir, cobicistat, and combinations thereof. In some embodiments, the antiviral agent is selected from the group consisting of saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, darunavir, tipranavir, and combinations thereof. In some embodiments, the protease inhibitor is a HCV NS3/4A protease inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of voxilaprevir, asunaprevir, boceprevir, paritaprevir, simeprevir, telaprevir, vaniprevir, grazoprevir, ribavirin, danoprevir, faldaprevir, vedroprevir, sovaprevir, deldeprevir, narlaprevir and combinations thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of voxilaprevir, asunaprevir, boceprevir, paritaprevir, simeprevir, telaprevir, vaniprevir, grazoprevir, and combinations thereof. In some embodiments, the protease inhibitor is PF-07321332, having the structure: [00141] PF-07321332 acts an orally active 3CL protease inhibitor, and the combination of PF-07321332 with ritonavir is in phase III trials for the treatment of COVID-19. In some embodiments, the protease inhibitor is lenacapavir (GS-6207) that is being developed by Gilead Sciences for the treatment of HIV. It has the structure: [00142] In some embodiments, the additional therapeutic agent is an integrase inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of raltegravir, dolutegravir, elvitegravir, abacavir, lamivudine, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of bictegravir, raltegravir, dolutegravir, cabotegravir, elvitegravir, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of bictegravir, dolutegravir, and cabotegravir, and combinations thereof. In some embodiments, the additional therapeutic agent is bictegravir. [00143] In some embodiments, the additional therapeutic agent is an entry inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of docosanol, enfuvirtide, maraviroc, ibalizumab, fostemsavir, leronlimab, ibalizumab, fostemsavir, leronlimab, palivizumab, respiratory syncytial virus immune globulin, intravenous [RSV-IGIV], varicella-zoster immunoglobulin [VariZIG], varicella- zoster immune globulin [VZIG]), and combinations thereof. [00144] In some embodiments, the additional therapeutic agent is an acyclic guanosine analogue. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of acyclovir, ganciclovir, valacyclovir (also known as valaciclovir), valganciclovir, penciclovir, famciclovir, and combinations thereof. [00145] In some embodiments, the additional therapeutic agent is an acyclic nucleoside phosphonate analogues. For example, in some embodiments, the additional therapeutic agent is selected from a group consisting of cidofovir, adefovir, adefovir dipivoxil, tenofovir, TDF, emtricitabine, efavirenz, rilpivirine, elvitegravir, and combinations thereof. In some embodiment, the additional therapeutic agent is selected from the group consisting of cidofovir, adefovir, adefovir dipivoxil, tenofovir, TDF, and combinations thereof. In some embodiment, the additional therapeutic agent is selected from the group consisting of cidofovir, adefovir dipivoxil, TDF, and combinations thereof. [00146] In some embodiments, the additional therapeutic agent is a HCV NS5A or NS5B inhibitor. In some embodiments, the additional therapeutic agent is a NS3/4A protease inhibitor. In some embodiments, the additional therapeutic agent is a NS5A protein inhibitor. In some embodiments, the additional therapeutic agent is a NS5B polymerase inhibitor of the nucleoside/nucleotide type. In some embodiments, the additional therapeutic agent is a NS5B polymerase inhibitor of the nonnucleoside type. In some embodiments, the additional therapeutic agent is selected from the group consisting of daclatasvir, ledipasvir, velpatasvir, ombitasvir, elbasvir, sofosbuvir, dasabuvir, ribavirin, asunaprevir, simeprevir, paritaprevir, ritonavir, elbasvir, grazoprevir, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of daclatasvir, ledipasvir, velpatasvir, ombitasvir, elbasvir, sofosbuvir, dasabuvir, and combinations thereof. [00147] In some embodiments, the additional therapeutic agent is an influenza virus inhibitor. [00148] In some embodiments, the additional therapeutic agents is a matrix 2 inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of amantadine, rimantadine, and combinations thereof. In some embodiments, the additional therapeutic agent is a neuraminidase inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of zanamivir, oseltamivir, peramivir, laninamivir octanoate, and combinations thereof. In some embodiments, the additional therapeutic agent is a polymerase inhibitor distinct from the compounds of the present invention. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of ribavirin, favipiravir, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of amantadine, rimantadine, arbidol (umifenovir), baloxavir marboxil, oseltamivir, peramivir, ingavirin, laninamivir octanoate, zanamivir, favipiravir, ribavirin, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of amantadine, rimantadine, zanamivir, oseltamivir, peramivir, laninamivir octanoate, ribavirin, favipiravir, and combinations thereof. In some embodiments, the additional therapeutic agent is DAS-181 or XC-221. [00149] In some embodiments, the additional therapeutic agent is an interferon. In some embodiments, the additional therapeutic agent is selected from the group consisting of interferon alfacon 1, interferon alfa lb, interferon alfa 2a, interferon alfa 2b, pegylated interferon alfacon 1, pegylated interferon alfa lb, pegylated interferon alfa 2a (PegIFNα-2a), and PegIFNa-2b. [00150] In some embodiments, the additional therapeutic agent is selected from the group consisting of interferon alfacon 1, pegylated interferon alfa 2a (PegIFNa-2a), PegIFNa-2b, and ribavirin. In some embodiments, the additional therapeutic agent is pegylated interferon alfa-2a, pegylated interferon alfa-2b, or a combination thereof. In some examples, the additional therapeutic agent is interferon-beta. For example, the additional therapeutic agent ls interfernn-beta-1 a, such as SNG-001. In some embodiments, the additional therapeutic agent is an inteferon--inducing agent, such as tilorone hydrochloride. In some embodiments, the additional therapeutic agent is IL-17 antagonist such as ixekizumab. In some embodiments, the additional therapeutic agent is interferon alfa 2 ligand, secukinumab, IMU- 838, or vidofludimus. [00151] In some embodiments, the additional therapeutic agent is an immunostimulatory agent. In some embodiments, the additional therapeutic agent is an oligonucleotide. In some embodiments, the additional therapeutic agent is an antimitotic inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of fomivirsen, podofilox, imiquimod, sinecatechins, and combinations thereof. In some embodiments, the additional therapeutic agent is azoximer bromide or IMM-101. [00152] In some embodiments, the additional therapeutic agent is selected from the group consisting of besifovir, nitazoxanide, REGN2222, doravirine, sofosbuvir, velpatasvir, daclatasvir, asunaprevir, beclabuvir, FVl00, and letermovir, and combinations thereof. [00153] In some embodiments, the additional therapeutic agent is an agent for treatment of RSV. For example, in some embodiments, the antiviral agent is ribavirin, ALS-8112 or presatovir. For example, in some embodiments, the antiviral agent is ALS-8112 or presatovir. [00154] In some embodiments, the antiviral agent is DFV890. In some embodiments, the antiviral agent is MAS825. In some embodiments, the antiviral agent is emetine. In some embodiments, the antiviral agent is protoporphyrin IX, SnPP protoporphyrin and verteporfin. In some embodiments, the antiviral agent is RBT-9. In some embodiments, the antiviral agent is thymosin. In some embodiments, the additional therapeutic agent is ivermectin. [00155] In some embodiments, the additional therapeutic agent is an agent for treatment of picomavirus. In some embodiments, the additional therapeutic agent is selected from the group consisting of hydantoin, guanidine hydrochloride, L-buthionine sulfoximine, Py-11, and combinations thereof. In some embodiments, the additional therapeutic agent is a picomavirus polymerase inhibitor. In some embodiments, the additional therapeutic agent is rupintrivir. [00156] In some embodiments, the additional therapeutic agent is an agent for treatment of malaria. For example, the additional therapeutic agent is dihydroartemisinin piperaquine. In some embodiments, the additional therapeutic agent is pyramax. [00157] In some embodiments, the additional therapeutic agent is selected from the group consisting of hydroxychloroquine, chloroquine, artemether, lumefantrine, atovaquone, proguanil, tafenoquine, pyronaridine, artesunate, artenimol, piperaquine, artesunate, amodiaquine, pyronaridine, artesunate, halofantrine, quinine sulfate, mefloquine, solithromycin, pyrimethamine, MMV-390048, ferroquine, artefenomel mesylate, ganaplacide, DSM-265, cipargamin, artemisone, and combinations thereof. [00158] In some embodiments, the additional therapeutic agent is an agent for treatment of coronavirus. In some embodiments, the additional therapeutic agent is selected from a group consisting of IFX-1, FM-201, CYNK-001, DPP4-Fc, ranpirnase, nafamostat, LB-2, AM-1, antiviroporins, and combinations thereof. [00159] In some embodiments, the additional therapeutic agent is an agent for treatment of ebola virus. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of ribavirin, palivizumab, motavizumab, RSV-IGIV (RespiGam®), MEDI-557, A-60444, MDT-637, BMS-433771, amiodarone, dronedarone, verapamil, Ebola Convalescent Plasma (ECP), TKM-100201, BCX4430 ((2S,3S,4R,5R)-2-(4-amino- 5Hpyrrolo[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)pyrrolidine -3,4-diol), favipiravir (also known as T-705 or Avigan), T-705 monophosphate, T-705 diphosphate, T-705 triphosphate, FGI-106 (l-N,7-N-bis[3-( dimethylamino )propyl]-3,9-dimethylquinolino[8, 7-h]quinolone- l,7-diamine), JK-05, TKM-Ebola, ZMapp, rNAPc2, VRC-EBOADC076-00-VP, OS-2966, MVA-BN filo, brincidofovir, Vaxart adenovirus vector 5-based ebola vaccine, Ad26- ZEBOV, Filo Vax vaccine, GOVX-E301, GOVX-E302, ebola virus entry inhibitors (NPCl inhibitors), rVSV-EBOV, and combinations thereof. In some embodiments, the additional therapeutic agent is ZMapp, mAB114, REGEN-EB3, and combinations thereof. [00160] In some embodiments, the additional therapeutic agent is an agent for treatment of HCV. In some embodiments, the additional therapeutic agent is a HCV polymerase inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of sofosbuvir, GS-6620, PSI-938 , ribavirin, tegobuvir, radalbuvir, MK- 0608, and combinations thereof. In some embodiments, the additional therapeutic agent is a HCV protease inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of such as GS-9256, vedroprevir, voxilaprevir, and combinations thereof. [00161] In some embodiments, the additional therapeutic agent is a NS5A inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of ledipasvir, velpatasvir, and combinations thereof. [00162] In some embodiments, the additional therapeutic agent is an anti HBV agent. For example, in some embodiments, the additional therapeutic agent is tenofovir disoproxil fumarate and emtricitabine, or a combination thereof. Examples of additional anti HBV agents include but are not limited to alpha-hydroxytropolones, amdoxovir, antroquinonol, beta-hydroxycytosine nucleosides,, ARB-199, CCC-0975, ccc-R08, elvucitabine, ezetimibe, cyclosporin A, gentiopicrin (gentiopicroside), HH-003, hepalatide, JNJ-56136379, nitazoxanide, birinapant, NJK14047, NOV-205 (molixan, BAM-205), oligotide, mivotilate, feron, GST-HG-131, levamisole, Ka Shu Ning, alloferon, WS-007, Y-101 (Ti Fen Tai), rSIFN-co, PEG-IIFNm, KW-3, BP-Inter-014, oleanolic acid, HepB-nRNA, cTP-5 (rTP-5), HSK-11-2, HEISCO-106-1, HEISCO-106, Hepbarna, IBPB-006IA, Hepuyinfen, DasKloster 0014-01, ISA-204, Jiangantai (Ganxikang), MIV-210, OB-AI-004, PF-06, picroside, DasKloster-0039, hepulantai, IMB-2613, TCM-800B, reduced glutathione, RO-6864018, RG-7834, QL-007sofosbuvir, ledipasvir, UB-551, and ZH-2N, and the compounds disclosed in US20150210682, (Roche), US 2016/0122344 (Roche), WO2015173164, WO2016023877, US2015252057A (Roche), WO16128335Al (Roche), WO16120186Al (Roche), US2016237090A (Roche), WO16107833Al (Roche), WO16107832Al (Roche), US2016176899A (Roche), WO16102438Al (Roche), WO16012470Al (Roche), US2016220586A (Roche), and US2015031687A (Roche). In some embodiments, the additional therapeutic agent is a HBV polymerase inhibitor. Examples of HBV DNA polymerase inhibitors include, but are not limited to, adefovir (HEPSERA®), emtricitabine (EMTRIVA®), tenofovir disoproxil fumarate (VIREAD®), tenofovir alafenamide, tenofovir, tenofovir disoproxil, tenofovir alafenamide fumarate, tenofovir alafenamide hemifumarate, tenofovir dipivoxil, tenofovir dipivoxil fumarate, tenofovir octadecyloxyethyl ester, CMX- 157, tenofovir exalidex, besifovir, entecavir (BARACLUDE®), entecavir maleate, telbivudine (TYZEKA®), filocilovir, pradefovir, clevudine, ribavirin, lamivudine (EPIVIRHBV®), phosphazide, famciclovir, fusolin, metacavir, SNC-019754, FMCA, AGX- 1009, AR-11-04-26, HIP-1302, tenofovir disoproxil aspartate, tenofovir disoproxil orotate, and HS-10234. [00163] In some embodiments, the additional therapeutic agent is a HBV capsid inhibitor. [00164] In some embodiments, the additional therapeutic agent is an agent for treatment of HIV. In some embodiments, the additional therapeutic agent is selected from the group consisting of HIV protease inhibitors, HIV integrase inhibitors, entry inhibitors, HIV nucleoside reverse transcriptase inhibitors, HIV nonnucleoside reverse transcriptase inhibitors, acyclic nucleoside phosphonate analogues, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of HIV protease inhibitors, HIV non-nucleoside or non-nucleotide inhibitors of reverse transcriptase, HIV nucleoside or nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, HIV non-catalytic site (or allosteric) integrase inhibitors, HIV entry inhibitors, HIV maturation inhibitors, immunomodulators, immunotherapeutic agents, antibody drug conjugates, gene modifiers, gene editors (such as CRISPR/Cas9, zinc finger nucleases, homing nucleases, synthetic nucleases, TALENs), and cell therapies (such as chimeric antigen receptor T-cell, CAR-T, and engineered T cell receptors, TCR-T, autologous T cell therapies). In some embodiments, the additional therapeutic agent is an immunotherapeutic peptides such as tertomotide. In some embodiments, the additional therapeutic agent is a CCL26 gene inhibitor, such as mosedipimod. [00165] In some embodiments, the additional therapeutic agent is selected from the group consisting of combination drugs for HIV, other drugs for treating HIV, HIV protease inhibitors, HIV reverse transcriptase inhibitors, HIV integrase inhibitors, HIV non-catalytic site (or allosteric) integrase inhibitors, HIV entry (fusion) inhibitors, HIV maturation inhibitors, latency reversing agents, capsid inhibitors, immune-based therapies, PI3K inhibitors, HIV antibodies, and bispecific antibodies, and "antibody-like" therapeutic proteins, and combinations thereof. In some embodiments, the additional therapeutic agent is a PI3K inhibitor, for example idelalisib or duvelisib. [00166] In some examples, the additional therapeutic agent is a HIV combination drug. Examples of the HIV combination drugs include, but are not limited to ATRIPLA® (efavirenz, tenofovir disoproxil fumarate, and emtricitabine); BIKTARVY® (bictegravir, emtricitabine, and tenofovir alafenamide); COMPLERA® (EVIPLERA®; rilpivirine, tenofovir disoproxil fumarate, and emtricitabine ); STRIBILD® (elvitegravir, cobicistat, tenofovir disoproxil fumarate, and emtricitabine); TRUV ADA® (tenofovir disoproxil fumarate and emtricitabine; TDF+FTC); DESCOVY® (tenofovir alafenamide and emtricitabine); ODEFSEY® (tenofovir alafenamide, emtricitabine, and rilpivirine); GENVOYA® (tenofovir alafenamide, emtricitabine, cobicistat, and elvitegravir); SYMTUZA® (darunavir, tenofovir alafenamide hemifumarate, emtricitabine, and cobicistat); SYMFI™ (efavirenz, lamivudine, and tenofovir disoproxil fumarate); CIMDU™ (lamivudine and tenofovir disoproxil fumarate); tenofovir and lamivudine; tenofovir alafenamide and emtricitabine; tenofovir alafenamide hemifumarate and emtricitabine; tenofovir alafenamide hemifumarate, emtricitabine, and rilpivirine; tenofovir alafenamide hemifumarate, emtricitabine, cobicistat, and elvitegravir; COMBIVIR® (zidovudine and lamivudine; AZT +3TC); EPZICOM® (LIVEXA®; abacavir sulfate and lamivudine; ABC+3TC); KALETRA® (ALUVIA ®; lopinavir and ritonavir); TRIUMEQ® (dolutegravir, abacavir, and lamivudine); TRIZIVIR® (abacavir sulfate, zidovudine, and lamivudine; ABC+AZT +3TC); atazanavir and cobicistat; atazanavir sulfate and cobicistat; atazanavir sulfate and ritonavir; darunavir and cobicistat; dolutegravir and rilpivirine; dolutegravir and rilpivirine hydrochloride; dolutegravir, abacavir sulfate, and lamivudine; lamivudine, nevirapine, and zidovudine; raltegravir and lamivudine; doravirine, lamivudine, and tenofovir disoproxil fumarate; doravirine, lamivudine, and tenofovir disoproxil; dapivirine + levonorgestrel, dolutegravir + lamivudine, dolutegravir + emtricitabine + tenofovir alafenamide, elsulfavirine + emtricitabine + tenofovir disoproxil, lamivudine + abacavir + zidovudine, lamivudine + abacavir, lamivudine + tenofovir disoproxil fumarate, lamivudine + zidovudine + nevirapine, lopinavir + ritonavir, lopinavir + ritonavir + abacavir + lamivudine, lopinavir + ritonavir + zidovudine + lamivudine, tenofovir + lamivudine, and tenofovir disoproxil fumarate + emtricitabine + rilpivirine hydrochloride, lopinavir , ritonavir, zidovudine and lamivudine. [00167] In some embodiments, the additional therapeutic agent is a HIV protease inhibitor. For example, in some embodiments the additional therapeutic agent is selected from the group consisting of saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, darunavir, tipranavir, cobicistat, ASC-09, AEBL-2, MK-8718, GS-9500, GS-1156, and combinations thereof. For example, in some embodiments the additional therapeutic agent is selected from the group consisting of saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, darunavir, tipranavir, cobicistat. In some examples, the additional therapeutic agent is selected from the group consisting of amprenavir, atazanavir, brecanavir, darunavir, fosamprenavir, fosamprenavir calcium, indinavir, indinavir sulfate, lopinavir, nelfinavir, nelfinavir mesylate, ritonavir, saquinavir, saquinavir mesylate, tipranavir, DG-17, TMB-657 (PPL-100), T-169, BL-008, MK-8122, TMB-607, TMC-310911, and combinations thereof. [00168] In some embodiments, the additional therapeutic agent is a HIV integrase inhibitor. For example, in some embodiment, the additional therapeutic agent is selected from the group consisting of raltegravir, elvitegravir, dolutegravir, abacavir, lamivudine, bictegravir and combinations thereof. In some embodiment, the additional therapeutic agent is bictegravir. In some examples, the additional therapeutic agent is selected from a group consisting of bictegravir, elvitegravir, curcumin, derivatives of curcumin, chicoric acid, derivatives of chicoric acid, 3,5-dicaffeoylquinic acid, derivatives of 3,5-dicaffeoylquinic acid, aurintricarboxylic acid, derivatives of aurintricarboxylic acid, caffeic acid phenethyl ester, derivatives of caffeic acid phenethyl ester, tyrphostin, derivatives of tyrphostin, quercetin, derivatives of quercetin, raltegravir, dolutegravir, JTK-351, bictegravir, AVX- 15567, BMS-986197, cabotegravir (long acting injectable), diketo quinolin-4-1 derivatives, integrase-LEDGF inhibitor, ledgins, M-522, M-532, NSC-310217, NSC-371056, NSC- 48240, NSC-642710, NSC-699171, NSC-699172, NSC-699173, NSC-699174, stilbenedisulfonic acid, T-169, VM-3500, cabotegravir, and combinations thereof. [00169] In some embodiments, the additional therapeutic agent is a HIV entry inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of enfuvirtide, maraviroc, and combinations thereof. Further examples of HIV entry inhibitors include, but are not limited to, cenicriviroc, CCR5 inhibitors, gp41 inhibitors, CD4 attachment inhibitors, DS-003 (BMS-599793), gp120 inhibitors, and CXCR4 inhibitors. [00170] Examples of CCR5 inhibitors include aplaviroc, vicriviroc, maraviroc, cenicriviroc, leronlimab (PRO-140), adaptavir (RAP-101), nifeviroc (TD-0232), anti- GP120/CD4 or CCR5 bispecific antibodies, B-07, MB-66, polypeptide C25P, TD-0680, and vMIP (Haimipu). Examples of CXCR4 inhibitors include plerixafor, ALT-1188, N15 peptide, and vMIP (Haimipu). [00171] In some embodiments, the additional therapeutic agent is a HIV nucleoside reverse transcriptase inhibitors. In some embodiments, the additional therapeutic agent is a HIV non-nucleoside reverse transcriptase inhibitors. In some embodiments, the additional therapeutic agent is an acyclic nucleoside phosphonate analogue. In some embodiments, the additional therapeutic agent is a HIV capsid inhibitor. [00172] In some embodiments, the additional therapeutic agent is a HIV nucleoside or nucleotide inhibitor of reverse transcriptase. For example, the additional therapeutic agent is selected from the group consisting of adefovir, adefovir dipivoxil, azvudine, emtricitabine, tenofovir, tenofovir alafenamide, tenofovir alafenamide fumarate, tenofovir alafenamide hemifumarate, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir disoproxil hemifumarate, VIDEX® and VIDEX EC® (didanosine, ddl), abacavir, abacavir sulfate, alovudine, apricitabine, censavudine, didanosine, elvucitabine, festinavir, fosalvudine tidoxil, CMX-157, dapivirine, doravirine, etravirine, OCR-5753, tenofovir disoproxil orotate, fozivudine tidoxil, islatravir, lamivudine, phosphazid, stavudine, zalcitabine, zidovudine, rovafovir etalafenamide (GS-9131), GS-9148, MK-8504, MK-8591, MK-858, VM-2500, KP- 1461, and combinations thereof. [00173] In some examples, the additional therapeutic agent is a HIV non-nucleoside or nonnucleotide inhibitor of reverse transcriptase. For example, the additional agent is selected from the group consisting of dapivirine, delavirdine, delavirdine mesylate, doravirine, efavirenz, etravirine, lentinan, MK-8583, nevirapine, rilpivirine, TMC-278LA, ACC-007, AIC-292, KM-023, PC-1005, elsulfavirine rilp (VM-1500), combinations thereof. [00174] In some embodiments, the additional therapeutic agents are selected from ATRIPLA® (efavirenz, tenofovir disoproxil fumarate, and emtricitabine); COMPLERA® (EVIPLERA®; rilpivirine, tenofovir disoproxil fumarate, and emtricitabine); STRIBILD® (elvitegravir, cobicistat, tenofovir disoproxil fumarate, and emtricitabine); TRUV ADA® (tenofovir disoproxil fumarate and emtricitabine; TDF +FTC); DESCOVY® (tenofovir alafenamide and emtricitabine); ODEFSEY® (tenofovir alafenamide, emtricitabine, and rilpivirine); GENVOYA® (tenofovir alafenamide, emtricitabine, cobicistat, and elvitegravir); adefovir; adefovir dipivoxil; cobicistat; emtricitabine; tenofovir; tenofovir disoproxil; tenofovir disoproxil fumarate; tenofovir alafenamide; tenofovir alafenamide hemifumarate; TRIUMEQ® (dolutegravir, abacavir, and lamivudine); dolutegravir, abacavir sulfate, and lamivudine; raltegravir; raltegravir and lamivudine; maraviroc; enfuvirtide; ALUVIA® (KALETRA®; lopinavir and ritonavir); COMBIVIR® (zidovudine and lamivudine; AZT +3TC); EPZICOM® (LIVEXA ®; abacavir sulfate and lamivudine; ABC+3TC); TRIZIVIR® (abacavir sulfate, zidovudine, and lamivudine; ABC+AZT +3TC); rilpivirine; rilpivirine hydrochloride; atazanavir sulfate and cobicistat; atazanavir and cobicistat; darunavir and cobicistat; atazanavir; atazanavir sulfate; dolutegravir; elvitegravir; ritonavir; atazanavir sulfate and ritonavir; darunavir; lamivudine; prolastin; fosamprenavir; fosamprenavir calcium efavirenz; etravirine; nelfinavir; nelfinavir mesylate; interferon; didanosine; stavudine; indinavir; indinavir sulfate; tenofovir and lamivudine; zidovudine; nevirapine; saquinavir; saquinavir mesylate; aldesleukin; zalcitabine; tipranavir; amprenavir; delavirdine; delavirdine mesylate; Radha-108 (receptol); lamivudine and tenofovir disoproxil fumarate; efavirenz, lamivudine, and tenofovir disoproxil fumarate; phosphazid; lamivudine, nevirapine, and zidovudine; abacavir; and abacavir sulfate. [00175] In some embodiments, the additional therapeutic agent is selected from the group consisting of colistin, valrubicin, icatibant, bepotastine, epirubicin, epoprosetnol, vapreotide, aprepitant, caspofungin, perphenazine, atazanavir, efavirenz, ritonavir, acyclovir, ganciclovir, penciclovir, prulifloxacin, bictegravir, nelfinavir, tegobuvi, nelfinavir, praziquantel, pitavastatin, perampanel, eszopiclone, and zopiclone. [00176] In some embodiments, the additional therapeutic agent is an inhibitor of Bruton tyrosine kinase (BTK, AGMXI, AT, ATK, BPK, IGHD3, IMDl, PSCTKl, XLA; NCBI Gene ID: 695). For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of (S )-6-amino-9-( l -(but-2-ynoy l)pyrrolidin-3-y 1)-7-( 4- phenoxypheny l)-7H-purin-8(9H)-one, acalabrutinib (ACP-196), BGB-3111, CB988, HM71224, ibrutinib (Imbruvica), M-2951 (evobrutinib), M7583, tirabrutinib (ONO-4059), PRN-1008, spebrutinib (CC-292), TAK-020, vecabrutinib, ARQ-531, SHR-1459, DTRMWXHS-12, TAS-5315, AZD6738, calquence, danvatirsen, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from a group consisting of tirabrutinib, ibrutinib, acalabrutinib, and combinations thereof. In some embodiments, the additional therapeutic agent is selected from a group consisting of tirabrutinib, ibrutinib, and combinations thereof. In some embodiments, the additional therapeutic agent is a receptor tyrosine kinase inhibitor (RTKI). In some embodiments, the additional therapeutic agent is tyrphostin A9 (A9). In some embodiments, the additional therapeutic agent is a TEK receptor tyrosine kinase inhibitor. In some embodiments, the additional therapeutic agent is abivertinib maleate (STI-5656). In some embodiments, the additional therapeutic agent is a tyrosine kinase inhibitor, such as masitinib. In some embodiments, the additional therapeutic agent is a sphingosine kinase-2 (sk2)inhibitor, such as opaganib. In some embodiments, the additional therapeutic agent is a kinase inhibitor such as pacritinib. In some embodiments, the additional therapeutic agent is an Axl tyrosine kinase receptor inhibitor, such as bemcentinib. In some embodiments, the additional therapeutic agent is a FYVE finger phosphoinositide kinase inhibitor. In some embodiments, the additional therapeutic agent is a checkpoint kinase inhibitor, such as prexasertib. In some embodiments, the additional therapeutic agent is a MAP kinase inhibitor, such as KTH-222, ATI-450. In some embodiments, the additional therapeutic agent is a mTOR inhibitor, such as sirolimus. In some embodiments, the additional therapeutic agent is a pi3k/ mTOR inhibitor such as dactolisib. In some embodiments, the additional therapeutic agent is a Hsp90 inhibitor, such as ganetespib, ADX- 1612. In some embodiments, the additional therapeutic agent is an MEK inhibitor such as ATR-002. In some embodiments, the additional therapeutic agent is a topoisomerase II inhibitor, such as etoposide. In some embodiments, the additional therapeutic agent is an exportin 1 inhibitor, such as selinexor, verdinexor. In some embodiments, the additional therapeutic agent is a dual inhibitor of PARPl/2 and Tankyrase 1/2, such as 2X-121. In some embodiments, the additional therapeutic agent is a cyclin dependent kinase inhibitor, such as CYC-065, CYC-202. In some embodiments, the additional therapeutic agent is a cytosine DNA methyltransferase inhibitor, such as decitabine. In some embodiments, the additional therapeutic agent is a DHFR inhibitor, such as methotrexate. In some embodiments, the additional therapeutic agent is a small ubiquitin related modifier inhibitor, such as TAK-981. In some embodiments, the additional therapeutic agent is an integrin agonist such as 7HP- 349. In some embodiments, the additional therapeutic agent is a BET inhibitor, such as apabetalone. In some embodiments, the additional therapeutic agent is a BRD4 inhibitor, such as CPI-0610, ABBV-744. In some embodiments, the additional therapeutic agent is a ERl inhibitor, such as toremifene. [00177] In some embodiments, the additional therapeutic agent is a KRAS inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of AMG-510, COTI-219, MRTX-1257, ARS-3248, ARS-853, WDB-178, BI- 3406, BI-1701963, ARS-1620 (Gl2C), SML-8-73-1 (Gl2C), Compound 3144 (Gl2D), Kobe0065/2602 (Ras GTP), RT11, MRTX-849 (Gl2C) and K-Ras(Gl2D)-selective inhibitory peptides, including KRpep-2 (Ac-RRCPLYISYDPVCRR-NH2), KRpep-2d (Ac-RRRRCPL YISYDPVCRRRR-NH2), and combinations thereof. [00178] In some embodiments, the additional therapeutic agent is an alkylating agent, such as melphalan. [00179] In some embodiments, the additional therapeutic agent is a proteasome inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from a group consisting of ixazomib, carfilzomib, marizomib, bortezomib, and combinations thereof. In some embodiments, the additional therapeutic agent is carfilzomib. [00180] In some embodiments, the additional therapeutic agent is a vaccine. For example, in some embodiments, the additional therapeutic agent is a DNA vaccine, RNA vaccine, live attenuated vaccine, therapeutic vaccine, prophylactic vaccine, protein based vaccine, or a combination thereof. In some embodiments, the additional therapeutic agent is mRNA-1273. In some embodiments, the additional therapeutic agent is INO-4800 or INO-4700. In some embodiments, the additional therapeutic agent is live-attenuated RSV vaccine MEDI-559, human monoclonal antibody REGN2222 against RSV, palivizumab, respiratory syncytial virus immune globulin, intravenous (RSV-IGIV), and combinations thereof. In some embodiments, the additional therapeutic agent is a HBV vaccine, for example pediarix, engerix-B, and recombivax HB. In some embodiments, the additional therapeutic agent is a VZV vaccine, for example zostavax and varivax. In some embodiments, the additional therapeutic agent is a HPV vaccine, for example cervarix, gardasil 9, and gardasil. In some embodiments, the additional therapeutic agent is an influenza virus vaccine. For example, a (i) monovalent vaccine for influenza A (e.g. influenza A (H5Nl) virus monovalent vaccine and influenza A (HlNl) 2009 virus monovalent vaccines), (ii) trivalent vaccine for influenza A and B viruses (e.g. Afluria, Agriflu, Fluad, Fluarix, Flublok, Flucelvax, FluLaval, Fluvirin, and Fluzone), and (iii) quadrivalent vaccine for influenza A and B viruses (FluMist, Fluarix, Fluzone, and FluLaval). In some embodiments, the additional therapeutic agent is a human adenovirus vaccine (e.g. Adenovirus Type 4 and Type 7 Vaccine, Live, Oral). In some embodiments, the additional therapeutic agent is a rotavirus vaccine (e.g. Rotarix for rotavirus serotype G 1, G3, G4, or G9 and RotaTeq for rotavirus serotype Gl, G2, G3, or G4). In some embodiments, the additional therapeutic agent is a hepatitis A virus vaccine (e.g. Havrix and Vaqta). In some embodiments, the additional therapeutic agent is poliovirus vaccines (e.g. Kinrix, Quadracel, and Ipol). In some embodiments, the additional therapeutic agent is a yellow fever virus vaccine (e.g. YFVax). In some embodiments, the additional therapeutic agent is a Japanese encephalitis virus vaccines ( e.g. Ixiaro and JE-Vax). In some embodiments, the additional therapeutic agent is a measles vaccine (e.g. M-M-R II and ProQuad). In some embodiments, the additional therapeutic agent is a mumps vaccine (e.g. M-M-R II and ProQuad). In some embodiments, the additional therapeutic agent is a rubella vaccine (e.g. M-M-R II and ProQuad). In some embodiments, the additional therapeutic agent is a varicella vaccine (e.g. ProQuad). In some embodiments, the additional therapeutic agent is a rabies vaccine (e.g. Imovax and RabAvert). In some embodiments, the additional therapeutic agent is a variola virus (smallpox) vaccine (ACAM2000). In some embodiments, the additional therapeutic agent is a and hepatitis E virus (HEV) vaccine (e.g. HEV239). In some embodiments, the additional therapeutic agent is a 2019-nCov vaccine. In some embodiments, the additional therapeutic agent is Ad5-nCoV. In some embodiments, the additional therapeutic agents in the mRNA vaccine BNT-162. In some embodiments, the additional therapeutic agent is a BCG vaccine. In some embodiments, the additional therapeutic agent is Pfizer-BioNTech COVID-19 vaccine. In some embodiments, the additional therapeutic agent is Moderna Covid-19 vaccine. In some embodiments, the additional therapeutic agent is AZD1222 (astrazeneca Covid-19 vaccine). In some embodiments, the additional therapeutic agent is a poliovirus vaccine, e.g. OPV. [00181] In some embodiments, the additional therapeutic agent is BNT162al, BNT162bl, BNT162b2, or BNT162c2 (prime/boost, single or multiple doses). In some embodiments, the additional agent is AZD1222 (ChAdOxl nCov-19) vaccine. In some embodiments, the additional agent is Gam-COVID-Vac (Ad26), Gam-COVID-Vac (Ad5), Gam-COVID-Vac (Ad26 Prime-boost), Covax-19, or Naso VAX. In some embodiments, the additional therapeutic agents is LUNAR-COV19 (ARCT-021). In some embodiments, the additional agent is TerraCoV2. In some embodiments, the additional agent is COVID-19 S-Trimer. In some embodiments, the additional agent is TNX-1810, TNX-1820, or TNX-1830. In some embodiments, the additional agent is VaxiPatch COVID-19 vaccine. In some embodiments, the additional agent is VBI-2901. In some embodiments, the additional agent is VLA-2001. In some embodiments, the additional agent is exoVACC-SARS-CoV2CoV-2. In some embodiments, the additional agent is SCB-2019. In some embodiments, the additional agent is MV-SARS-CoV-2. In some embodiments, the additional agent is NVX-CoV2373, Matrix- Mor NVX-CoV2373. In some embodiments, the additional agent is BBV152A, B, C, PicoVacc, KBP-COVID-19, MF59 adjuvanted SARS-CoV-2 Sclamp, MVC-COV1901, SCB-2019 (COVID-19 S-Trimer + CpG1018+AS03), TMV-083, V-591, VPM1002, or V- SARS. [00182] In some embodiments, the additional therapeutic agent is an antibody, for example a monoclonal antibody. For example, the additional therapeutic agent is an antibody against 2019-nCov selected from the group consisting of the Regeneron antibodies, the Wuxi Antibodies, the Vir Biotechnology Antibodies, antibodies that target the SARS-CoV-2 spike protein, antibodies that can neutralize SARS-CoV-2 (SARS-CoV-2 neutralizing antibodies), and combinations thereof. In some embodiments, the additional therapeutic agent is anti- SARS CoV antibody CR-3022. In some embodiments, the additional therapeutic agent is aPD-1 antibody. In some embodiments, the additional therapeutic agent is anti-IL-6R mAb. For example, the additional therapeutic agent is TZLS-501 or siltuximab. In some embodiments, the additional therapeutic agent is an antibody that targets specific sites on ACE2. In some embodiments, the additional therapeutic agent is a polypeptide targeting SARS-CoV-2 spike protein (S-protein). In some embodiments, the additional therapeutic agent is a virus suppressing factor (VSF, HzVSFv13). [00183] In some embodiments, the additional therapeutic agent is an anti-CD147 antibody. For example, the additional therapeutic agent is meplazumab. [00184] In some embodiments, the additional therapeutic agent is a phosphodiesterase type 4 (PDE4) or phosphodiesterase type 5 (PDE5) inhibitor. In some embodiments, the additional therapeutic agent is a PDE5 inhibitor, for example, the additional therapeutic agent is sildenafil. In some embodiments, the additional therapeutic agent is a PDE4 inhibitor, for example, the additional therapeutic agent is brilacidin. [00185] In some embodiments, the additional therapeutic agent is an agent targeting NKGA2. In some embodiments, the additional therapeutic agent is a checkpoint inhibitor. In some embodiments, the additional therapeutic agent is NKG2 A B activating NK receptor antagonist, such as monalizumab. In some examples, the additional therapeutic agent is a CTLA-4 checkpoint inhibitor, such as BPI-002. [00186] In some embodiments, the additional therapeutic agent is a CD73 antagonist, such as CPI-006. In some embodiments, the additional therapeutic agent is recombinant cytokine gene derived protein injection. [00187] In some embodiments, the additional therapeutic agent is a polymerase inhibitor. In some embodiments, the additional therapeutic agent is a DNA polymerase inhibitor. For example, in some embodiments, the additional therapeutic agent is cidofovir. In some embodiments, the additional therapeutic agent is lamivudine. In some embodiments, the additional therapeutic agent is a RNA polymerase inhibitor. For example, in some embodiments, the additional therapeutic agent is selected from the group consisting of ribavirin, favipiravir, lamivudine, pimodivir and combination thereof. In some embodiments, the additional therapeutic agent is selected from the group consisting of ribavirin, favipiravir, pimodivir and combinations thereof. [00188] In some embodiments, the additional therapeutic agent is selected from the group consisting of lopinavir, ritonavir, interferon-alpha-2b, ritonavir, arbidol, hydroxychloroquine, darunavir and cobicistat, abidol hydrochloride, oseltamivir, litonavir, emtricitabine, tenofovir alafenamide fumarate, baloxavir marboxil, ruxolitinib, and combinations thereof. [00189] In some embodiments, the additional therapeutic agent is a beta-catenin inhibitor. For example, the additional therapeutic agent is tetrandrine. [00190] In some embodiments, the additional therapeutic agent is a trypsin inhibitor, for example the additional therapeutic agent is ulinastatin. In some embodiments, the additional therapeutic agent is TAK-671. [00191] In some embodiments, the additional therapeutic agent is selected from the group consisting of ABBV-744, dBET6, MZl, CPI-0610, Sapanisertib, Rapamycin, Zotatifin, Verdinexor, Chloroquine, Dabrafenib, WDB002, Sanglifehrin A, FK-506, Pevonedistat, Ternatin 4, 4E2RCat, Tomivosertib, PS3061, IHVR-19029, Captopril, Lisinopril, Camostat, N afamostat, Chloramphenicol, Tigecycline, Linezolid, and combinations thereof. [00192] In some embodiments, the additional therapeutic agent is selected form the group consisting of JQ-1, RVX-208,silmitasertib, TMCB, apicidin, valproic acid, Bafilomycin Al, E-52862, PD-144418, RS-PPCC, PD28, haloperidol, entacapone, indomethacin, Metformin, Ponatinib, H-89, Merimepodib, Migalastat, Mycophenolic acid, Ribavirin, XL413, CCT 365623, Midostaurin, Ruxolitinib, ZINC I 775962367, ZINC4326719, ZINC4511851, ZINC95559591, AC-55541, AZ8838, Daunorubicin, GB llO, S-verapamil, AZ3451, and combinations thereof. [00193] In some embodiments, the additional therapeutic agent is selected form a group consisting of tilorone, cyclosporine, loperamide, mefloquine, amodiaquine, proscillaridin, digitoxin, digoxin, hexachlorophene, hydroxyprogesterone caproate, salinomycin, ouabain, cepharanthine, ciclesonide, oxyclozanide, anidulafungin, gilteritinib, berbamine, tetrandrine, abemaciclib, ivacaftor, bazedoxifene, niclosamide, eltrombopag, and combinations thereof. [00194] In some embodiments, the additional therapeutic agent is a drug targeting the coronavirus main protease 3CLpro (e.g. lopinavir). In some embodiments the additional therapeutic agent is a drug targeting the papain-like protease PLpro (e.g., lopinavir). In some examples, the additional therapeutic agent is a drug that functions as a virus-host cell fusion inhibitor to prevent viral entry into host cells (e.g. arbidol). In some embodiments, the additional therapeutic agent is a TMPRSS2 inhibitor (e.g. camostat mesylate). [00195] In some embodiments, the additional therapeutic agent is a serine protease inhibitor, such as LB ll 48, upamostat, RHB-107, or alpha- I antitrypsin. [00196] In some embodiments, the additional therapeutic agent is an inhibitor of neutrophil elastase, such as lonodelestat. [00197] In some embodiments, the additional therapeutic agent is an a-ketoamide. [00198] In some examples, the additional therapeutic agent is a poly-ADP-ribose polymerase 1 (PARPl) inhibitor, for example, the additional therapeutic agent is CVL218. [00199] In some embodiments, the additional therapeutic agent is selected from the group consisting of 6' -fluorinated aristeromycin analogues, acyclovir fleximer analogues, disulfiram, thiopurine analogues, ASC09F, GC376, GC813, phenylisoserine derivatives, neuroiminidase inhibitor analogues, pyrithiobac derivatives, bananins and 5- hydroxychromone derivatives, SSYAl0-001, griffithsin, HR2P-Ml, HR2P-M2, P21S10, Dihydrotanshinone E-64-C and E-64-D, OC43-HR2P, MERS-5HB, 229E-HR1P, 229E- HR2P, resveratrol, l-thia-4-azaspiro[4.5]decan-3-one derivatives, gemcitabine hydrochloride, loperamide, recombinant interferons, cyclosporine A, alisporivir, imatinib mesylate, dasatinib, selumetinib, trametinib, rapamycin, saracatinib, chlorpromazine, triflupromazine, fluphenazine, thiethylperazine, promethazine, cyclophilin inhibitors, Kll 777, camostat, k22, teicoplanin derivatives, benzo-heterocyclic amine derivatives N30, mycophenolic acid, silvestrol, and combinations thereof. [00200] In some embodiments, the additional therapeutic agent is an antibody. In some embodiments, the additional therapeutic agent is an antibody that binds to a coronavirus, for example an antibody that binds to SARS or MERS. In some embodiments, the additional therapeutic agent is a of 2019-nCoV virus antibody. [00201] In some embodiments, the additional therapeutic agent is LY-CoV555. In some embodiments, the additional therapeutic agent is S309. In some embodiments, the additional therapeutic agent is SAB-185. In some embodiments, the additional therapeutic agent is CB6. In some embodiments, the additional therapeutic agent is STI-1499. In some embodiments, the additional therapeutic agent is JS016. In some embodiments, the additional therapeutic agent is VNAR. In some embodiments, the additional therapeutic agent is VIR-7832 and/or VIR-7831. In some embodiments, the additional therapeutic agent is REGN-COV2 (REGN10933 + RGN10987) In some embodiments, the additional therapeutic agent is BAT2020, BAT2019. In some embodiments, the additional therapeutic agent is 47D 11. In some embodiments, the additional therapeutic agent is COVI-SHIELD. In some embodiments, the additional therapeutic agent is BRII-196, BRII-198. In some embodiments, the additional therapeutic agent is INM-005, SCTA0l, TY-027, XAV-19. [00202] Compositions of the invention are also used in combination with other active ingredients. For the treatment of 2019-nCoV virus infections, preferably, the other active therapeutic agent is active against coronavirus infections, for example 2019-nCoV virus infections. The compounds and compositions of the present invention are also intended for use with general care provided patients with 2019-nCoV viral infections, including parenteral fluids (including dextrose saline and Ringer's lactate) and nutrition, antibiotic (including metronidazole and cephalosporin antibiotics, such as ceftriaxone and cefuroxime) and/or antifungal prophylaxis, fever and pain medication, antiemetic (such as metoclopramide) and/or antidiarrheal agents, vitamin and mineral supplements (including Vitamin Kand zinc sulfate), anti-inflammatory agents ( such as ibuprofen or steroids), corticosteroids such as methylprednisolone, immonumodulatory medications (eg interferon), other small molecule or biologics antiviral agents targeting 2019-nCoV (such as but not limited to lopinavir/ritonavir, EIDD-1931, favipiravir, ribavirine, neutralizing antibodies, etc), vaccines, pain medications, and medications for other common diseases in the patient population, such anti-malarial agents (including artemether and artesunate-lumefantrine combination therapy), typhoid (including quinolone antibiotics, such as ciprofloxacin, macrolide antibiotics, such as azithromycin, cephalosporin antibiotics, such as ceftriaxone, or aminopenicillins, such as ampicillin), or shigellosis. In some embodiments, the additional therapeutic agent is dihydroartemisinin/piperaquine. In some embodiments, the additional therapeutic agent is a corticosteroid, for example the additional therapeutic agent is ciclesonide. In some embodiments, the compounds disclosed herein are used in combination with amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, cholecalciferol, vitamin C, prednisone, mometasone, or budenoside. [00203] In some embodiments, the compounds disclosed herein are used in combination with inhibitors such as Panaphix (PAX-1), which inhibit production of pro-inflammatory cytokines. In some embodiments, the compounds disclosed herein are used in combination with inhibitors such as NCP-112 which inhibit excessive immune response such as cytokine storm. [00204] In some embodiments, the additional therapeutic agent is an antifungal agent, for example itraconazole or 17-0H- itraconazole. [00205] In some examples, the additional therapeutic agent is an immunomodulator. Examples of immune-based therapies include toll-like receptors modulators such as tlrl, tlr2, tlr3, tlr4, tlr5, tlr6, tlr7, tlr8, tlr9, tlrlO, tlrll, tlr12, and tlr13; programmed cell death protein 1 (Pd-1) modulators; programmed death-ligand 1 (Pd-Ll) modulators; IL-15 modulators; DermaVir; interleukin-7; plaquenil (hydroxychloroquine); proleukin (aldesleukin, IL-2); interferon alfa; interferon alfa-2b; interferon alfa-n3; pegylated interferon alfa; interferon gamma; hydroxyurea; mycophenolate mofetil (MPA) and its ester derivative mycophenolate mofetil (MMF); ribavirin; polymer polyethyleneimine (PEI); gepon; IL-12; WF-10; VGV-1; MOR-22; BMS-936559; CYT-107, interleukin-15/Fc fusion protein, AM-0015, ALT-803, NIZ-985, NKTR-255, NKTR-262, NKTR-214, normferon, peginterferon alfa-2a, peginterferon alfa-2b, recombinant interleukin-15, Xmab-24306, RPI-MN, STING modulators, RIG-I modulators, NOD2 modulators, SB-9200, and IR-103. In some embodiments, the additional therapeutic agent is fingolimod, leflunomide, or a combination thereof. In some embodiments, the additional therapeutic agent is thalidomide. In some embodiments, the additional therapeutic agent is CD24Fc. In some embodiments, the additional therapeutic agent is a type I IL-1 receptor antagonists, such as anakinra. In some embodiments, the additional therapeutic agent is a TLR4 antagonist, such as EB-05. [00206] In some embodiments, the additional therapeutic agent is nivolumab, efineptakin alfa, lactoferrin, ozanimod, astegolimab (MSTT1041A, RG-6149), or UTTR1147 A. In some embodiments, the additional therapeutic agent is Ampligen. In some embodiments, the additional therapeutic agent is lefitolimod. In some embodiments, the additional therapeutic agent is RPH-104. In some embodiments, the additional therapeutic agent is canakinumab. In some embodiments, the additional therapeutic agent is an IL-33 ligand inhibitor such as MEDI3506. In some embodiments, the additional therapeutic agent is an IL-5 receptor antagonist, such as mepolizumab. In some embodiments, the additional therapeutic agent is an IL-12 inhibitor, such as apilimod. In some embodiments, the additional therapeutic agent is a IL-15 receptor agonist, such as N-803. [00207] In some embodiments, the additional therapeutic agent is an interferon gamma ligand inhibitor, such as emapalumab. [00208] In some embodiments, the additional therapeutic agent is an IL-6 inhibitor, for example tocilizumab, sarilumab, or a combination thereof. In some embodiments, the additional therapeutic agent is tocilizumab. In some embodiments, the additional therapeutic agent is an IL-6 inhibitor, for example tocilizumab, sarilumab, olokizumab, sirukumab, clazakizumab, levilimab or a combination thereof. [00209] In some embodiments, the additional therapeutic agent is a nicotinamide phosphoribosyltransferase inhibitors. For example, the additional therapeutic agent is enamptcumab. [00210] In some embodiments, the additional therapeutic agent is a di peptidase 1 (DPEP- 1) inhibitor. For example, the additional therapeutic agent is Metablok (LSALT peptide). [00211] In some embodiments, the additional therapeutic agent is an anti-TNF inhibitor. For example, the additional therapeutic agent is adalimumab, etanercept, golirnurnab, infliximab, or a combination thereof. In some embodiments, the additional therapeutic agent is a TNF alpha ligand inhibitor, such as XPro1595. [00212] In some embodiments, the additional therapeutic agent is a JAK inhibitor, for example the additional therapeutic agent is baricitinib, filgotinib, olumiant, or a combination thereof. In some examples, the additional therapeutic agent is jaktinib. In some embodiments, the additional therapeutic agent is tofacitinib or TD-0903. [00213] In some embodiments, the additional therapeutic agent is an inflammation inhibitor, for example pirfenidone. In some embodiments, the additional therapeutic agent is L YT-100. [00214] In some embodiments, the additional therapeutic agent is an anti-inflammatory agent, such as dociparstat sodium. In some embodiments, the additional agent is used in the treatment of septic shock, such as nangibotide. In some embodiments, the additional therapeutic agent is a CCRl antagonist, such as MLN-3897. In some embodiments, the additional therapeutic agent targets IKKβ and NFKβ, such as OP-101. In some embodiment, the additional therapeutic agent is a glucocorticoid receptor agonist, such as hydrocortisone or dexamethasone. In some embodiments, the additional therapeutic agent is an immunosuppressant, such as tacrolimus, BXT-10, ibudilast, FP-025, apremilast, abatacept, crizanlizumab, itolizumab, bardoxolone methyl, M-5049. In some embodiments, the additional therapeutic agent is a RIP-1 kinase inhibitor, such as DNL-758. In some embodiments, the additional therapeutic agent is a IL-8 receptor antagonist, such as BMS- 986253 (HuMax-IL8). In some embodiments, the additional therapeutic agent is a CD 14 inhibitor, such as IC-14. In some embodiments, the additional therapeutic agent is a Dihydroorotate dehydrogenase (DHODH) inhibitor, such as brequinar, PCT-299. In some embodiments, the additional therapeutic is anti-fibrotic, such as RT-1840,nintedanib, GB- 0139, nintedanib, pamrevlumab. In some embodiments, the additional therapeutic is a hepatocyte growth factor (HGF) mimetic, such as SNV-003 (ANG-3777). [00215] In some embodiments, the additional therapeutic agent is an A3 adenosine receptor (A3AR) antagonist, for example the additional therapeutic agent is piclidenoson. [00216] In some embodiments, the additional therapeutic agent is an antibiotic for secondary bacterial pneumonia. For example, the additional therapeutic agent is macrolide antibiotics (e.g. azithromycin, clarithromycin, and mycoplasma pneumoniae), fluoroquinolones (e.g. ciprofloxacin and levofloxacin), tetracyclines (e.g. doxycycline and tetracycline), or a combination thereof. In some embodiments, the additional therapeutic agent is XEL 1004. In some embodiments, the additional therapeutic agent is eravacycline. [00217] In some embodiments, the compounds disclosed herein are used in combination with pneumonia standard of care (see e.g. Pediatric Community Pneumonia Guidelines, CID 2011:53 (1 October)). Treatment for pneumonia generally involves curing the infection and preventing complications. Specific treatment will depend on several factors, including the type and severity of pneumonia, age and overall health of the individuals. The options include: (i) antibiotics, (ii) cough medicine, and (iii) fever reducers/pain relievers (for e.g. aspirin, ibuprofen (Advil, Motrin IB, others) and acetaminophen (Tylenol, others)). In some embodiments, the additional therapeutic agent is bromhexine anti-cough. [00218] In some embodiments, the compounds disclosed herein are used in combination with immunoglobulin from cured COVID-19 patients. In some embodiments, the compounds disclosed herein are used in combination with plasma transfusion. In some examples, the compounds disclosed herein are used in combination with TAK-888 (anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG)). In some embodiments, the compounds disclosed herein are used in combination with COVID-19 convalescent plasma or immunoglobulin. In some embodiments, the compounds described herein are used in combination with COVID- EIG or COVID-HIG. In some embodiments, the compounds disclosed herein are used in combination with stem cells. For example, in some embodiments, the compounds disclosed herein are used in combination with MultiStem or Remestemcel-L (mesenchymal stem cells). In some embodiments, the compounds described herein are used in combination with allogenic mesenchymal-like cells, for example in combination with PLX cells. In some embodiments, the compounds described herein are used in combination with allogenic cell therapy, for example in combination with CK-0802. In some embodiments, the compounds described herein are used in combination with Pluristem or ACT-20. [00219] In some examples, the additional therapeutic agent is an TLR agonist. Examples of TLR agonists include, but are not limited to, vesatolimod (GS-9620), GS-986, IR-103, lefitolimod, tilsotolimod, rintatolimod, DSP-0509, AL-034, G-100, cobitolimod, AST-008, motolimod, GSK-1795091, GSK-2245035, VTX-1463, GS-9688, LHC-165, BDB-001, RG- 7854, telratolimod.RO-7020531. In some embodiments the additional therapeutic agent is PUL-042. In some embodiments, the additional therapeutic agent is polyinosinic- polycytidylic acid (poly I:C). [00220] In some examples, the additional therapeutic agent is selected from the group consisting of bortezomid, flurazepam, ponatinib, sorafenib, paramethasone, clocortolone, flucloxacillin, sertindole, clevidipine, atorvastatin, cinolazepam, clofazimine, fosaprepitant, and combinations thereof. In some examples, the additional therapeutic agent is simvastatin or rosuvastatin. [00221] In some examples, the additional therapeutic agent is carrimycin, suramin, triazavirin, dipyridamole, bevacizumab, meplazumab, GD31 (rhizobium), NLRP inflammasome inhibitor, or a-ketoamine. In some embodiments, the additional therapeutic agent is recombinant human angiotensin-converting enzyme 2 (rhACE2). In some embodiments, the additional therapeutic agent is viral macrophage inflammatory protein (vMIP). [00222] In some embodiments, the additional therapeutic agent is a recombinant human angiotensin-converting enzyme 2 (rhACE2), for example APN-01. In some embodiments, the additional therapeutic agent is an angiotensin II receptor agonist. In some examples, the additional therapeutic agent is a partial agonist of A T2 or a partial antagonist of AT 1. In some embodiments, the additional therapeutic agent is L-163491. In some embodiments, the additional therapeutic agent is ACE2-Fc fusion protein, for example the additional therapeutic agent is STI-4398. In some embodiments, the additional therapeutic agent is valsartan, losartan, candesartan, eprosartan, irbesartan, olmesartan. In some embodiments, the additional therapeutic agent is VP-01, TXA-127. In some embodiments, the additional therapeutic agent is telmisartan. [00223] In some embodiments, the additional therapeutic agent is an ACE inhibitor, such as ramipril, captopril, enalapril, or lisonopril. In some embodiments, the additional therapeutic agent is an aldose reductase inhibitor, such as AT-001. [00224] In some embodiments, the additional therapeutic agent is a platelet inhibitor. For example, the additional therapeutic agent is dipyridamole. [00225] In some embodiments, the additional therapeutic agent is an anti-coagulant, such as heparins (heparin and low molecular weight heparin), aspirin, apixaban, dabigatran, edoxaban, argatroban, enoxaparin, fondaparinux. In some embodiments, the additional therapeutic agent is a tissue factor inhibitor, such as AB-201. In some embodiments, the additional therapeutic is a Factor Xlla antagonist, such as garadacimab. In some embodiments, the additional therapeutic agent is a VE-PTP inhibitor, such as razuprotafib. In some embodiments, the additional therapeutic agent is a VIP 2 receptor agonist, such as PB- 1046. In some embodiments, the additional therapeutic agent is an anti-thrombotic, such as defibrotide, rivaroxaban, alteplase, tirofiban, clopidogrel, prasugrel, bemiparin, bivalirudin, sulodexide, tranexamic acid. In some embodiments, the additional therapeutic agent is a vasodilator, such as iloprost, ventaprost, vazegepant, angiotensin 1-7, ambrisentan, NORS, pentoxifylline, propranolol, RESP301, sodium nitrite, TRV-027. In some embodiments, the additional therapeutic agent is a blood clotting modulator, such as lanadelumab. In some embodiments, the additional therapeutic agent is a diuretic, such as an aldosterone antagonist, such as spironolactone. In some embodiments, the additional therapeutic agent is antihypoxic, such as trans-sodium crocetinate. In some embodiments, the additional therapeutic agent is MK-5475. [00226] In some embodiments, the additional therapeutic agent is a hypoxia-inducible factor (HF) prolyl hydroxylase-2 (PHD-2) inhibitor such as desidustat or vadadustat. In some embodiments, the additional therapeutic agent is a renin inhibitor, such as aliskiren. In some embodiments, the additional therapeutic agent is a calcium channel inhibitor such as nifedipine. In some embodiments, the additional therapeutic agent is a chelating agent, such as desferal, deferiprone, deferoxamine. In some embodiments, the additional therapeutic agent is a retinoic acid receptor agonist, such as isotretinoin or fenretinide. In some embodiments, the additional therapeutic agent is an AMPA receptor modulator, such as traneurocin. In some embodiments, the additional therapeutic agent is a human antimicrobial peptide, such as LL-37i. In some embodiments, the additional therapeutic agent is a microbiome modulator, such as EDP-1815, KB-109. In some embodiments, the additional therapeutic agent is an estrogen receptor antagonist, such as tamoxifen. In some embodiments, the additional therapeutic agent is an androgen receptor antagonist such as bicalutamide, enzalutamide. [00227] In some embodiments, the additional therapeutic agent is a GNRH receptor antagonist, such as degarelix. In some embodiments, the additional therapeutic agent is a sex hormone modulator, such as dutasteride. In some embodiments, the additional therapeutic agent is a calpain inhibitor, such as BLD-2660. In some embodiments, the additional therapeutic agent is a GM-CSF ligand inhibitor such as gimsilumab, lenzilumab, namilumab, TJM2 or otilimab. In some embodiments, the additional therapeutic agent is a GM-CSF receptor antagonist, such as mavrilimumab. In some embodiments, the additional therapeutic agent is a GM-CSF receptor agonist, such as sargramostim. In some embodiments, the additional therapeutic agent is an alpha 1 adrenoreceptor antagonist such as prazosin. In some embodiments, the additional therapeutic agent is a neuropilin 2 inhibitor, such as ATYR- 1923. In some embodiments, the additional therapeutic agent is an activated calcium (CRAC) channel inhibitor, such as CM-4620. In some embodiments, the additional therapeutic agent is a proto-oncogene Mas agonist, such as BIO101. In some embodiments, the additional therapeutic agent is a DPP4 inhibitor, such as saxagliptin, sitagliptin, alogliptin, linagliptin. In some embodiments, the additional therapeutic agent is a sodium glucose cotransporter type 2 (SGLT-2) inhibitor such as dapagliflozin propanediol. In some embodiments, the additional therapeutic agent is a fractalkine receptor inhibitor such as KAND-567. [00228] In some embodiments, the additional therapeutic agent is an alpha2-receptor agonist. For example, the additional therapeutic agent is dexmedetomidine. [00229] In some embodiments, the additional therapeutic agent is a mCBM40 (multivalent carbohydrate-binding module Family 40 domain) product, for example the additional therapeutic agent is neumifil. [00230] In some embodiments, the additional therapeutic agent is a histamine H1 receptor antagonist, such as ebastine. In some embodiments, the additional therapeutic agent is tranilast. In some embodiments, the additional therapeutic agent is a histamine H2 receptor antagonist. In some embodiments, the additional therapeutic agent is famotidine. In some embodiments, the additional therapeutic agent is anti-histamine. In some embodiments, the additional therapeutic agent is cloroperastine or clemastine. [00231] In some embodiments, the additional therapeutic agent is a vasoactive intestinal peptide receptor 1 agonists, such as aviptadil. [00232] In some embodiments, the additional therapeutic agent is a drug that treats acute respiratory distress syndrome (ARDS). [00233] In some embodiments, the additional therapeutic agent is a peptide, for example the additional therapeutic agent is BIO-11006. In some embodiments, the additional therapeutic agent is aliposomal formulation, for example the additional therapeutic agent is LEAF-4L6715, LEAF-4L7520. In some embodiments, the additional therapeutic agent is a respiratory stimulant, such as almitrine. In some embodiments, the additional therapeutic agent is a bronchodilator, such as brensocatib or formoterol. In some embodiments, the additional therapeutic agent is an anti-LIGHT antibody, such as CERC-002. In some embodiments, the additional therapeutic agent is a CRAC (calcium release-activated calcium) channel inhibitor, such as CM-4620-IE. [00234] In some embodiments, the compounds described herein are used in combination with respiratory-specific small interfering RNA therapies. In some embodiments, these therapies are delivered by a nebulizer. [00235] In some embodiments, the additional therapeutic agent is a vimentin modulators. For example, the additional therapeutic agent is pritumumab. In some embodiments, the additional therapeutic agent is hzVSF-v13. [00236] In some embodiments, the additional therapeutic agent is a modulator of Nspl5 (nonstructural protein 15) such as benzopurpurin B, C-467929, C-473872, NSC-306711 and N-65828. [00237] In some embodiments, the additional therapeutic agent is a xanthine dehydrogenase inhibitor, such as oxypurinol (XRx-101). [00238] In some embodiments, the additional therapeutic agent is a cathepsin L-inhibitor. In some embodiments, the additional therapeutic agent is a cathepsin inhibitor, such as VBY- 825 or ONO-5334. [00239] In some embodiments, the additional therapeutic agent is a Transforming growth factor beta (TGF-~) inhibitor. For example, the additional therapeutic agent is OT-101. [00240] In some embodiments, the additional therapeutic agent is a N-methyl-D-aspartate (NMDA) receptor antagonist. For example, the additional therapeutic agent is ifenprodil. [00241] In some embodiments, the additional therapeutic agent is a glycolysis inhibitor. For example, the additional therapeutic agent is WP-1122. [00242] In some embodiments, the additional therapeutic is a Leukotriene D4 antagonist, such as montelukast. In some embodiments, the additional therapeutic is a Leukotriene BLT receptor antagonist, such as ebselen. In some embodiments, the additional therapeutic is a tubulin inhibitor, such as VERU-111 or colchicine. In some embodiments, the additional therapeutic agent is a glucosylceramide synthase inhibitor such as miglustat. In some embodiments, the additional therapeutic agent is a Nrf2 activator, such as PB 125. In some embodiments, the additional therapeutic agent is a Rev protein modulator, such as ABX464. In some embodiments, the additional therapeutic agent is a nuclear import inhibitor, such as iCP-NI (CV-15). In some embodiments, the additional therapeutic agent is a cannabinoid CB2 receptor agonist, such as PPP003. In some embodiments, the additional therapeutic agent is a dehydropeptidase-1 modulator, such as LSALT peptide. In some embodiments, the additional therapeutic agent is a cyclooxygenase inhibitor, such as celecoxib, naproxen, aspirin/dipyridamole. In some embodiments, the additional therapeutic agent is an antitoxin such as CAL02. In some embodiments, the additional therapeutic agent is a nitric oxide stimulant, such as GLS-1200. In some embodiments, the additional therapeutic agent is an apelin receptor agonist, such as CB-5064. In some embodiments, the additional therapeutic agent is a complement inhibitor, such as ravulizumab. In some embodiments, the additional therapeutic agent is a colony-stimulating factor 1 receptor (CSFlR) inhibitor, such as avdoralimab. In some embodiments, the additional therapeutic agent is a complement C5 factor inhibitor, such as eculizumab, zilucoplan, and C5a such as BDB-001, IFX-1, advoralimab, In some embodiments, the additional therapeutic agent is a complement C 1 s inhibitor, such as cone stat alpha. In some embodiments, the additional therapeutic agent is a C3 inhibitor, such as APL-9 or AMY-101. In some embodiments, the additional therapeutic agent is an anti-C5aR antibody, such as advoralimab. In some embodiments, the additional therapeutic agent is an anti-elongation factor 1 alpha 2 inhibitor, such as plitidepsin. In some embodiments, the additional therapeutic agent is an angiopoietin ligand-2 inhibitor, such as L Y-3127804. In some embodiments, the additional therapeutic agent is a lysine specific histone demethylase 1 inhibitor, such as vafidemstat. In some embodiments, the additional therapeutic agent is a hyaluronan inhibitor. In some embodiments, the additional therapeutic agent is a proton pump inhibitor, such as omeprazole. [00243] In some embodiments, the additional therapeutic agent is an anti-viroporin therapeutic. For example, the additional therapeutic agent is BIT-314 or BIT-225. In some embodiments, the additional therapeutic agent is coronavirus E protein inhibitor. For example, the additional therapeutic agent is BIT-009. Further examples of additional therapeutic agents include those described in WO-2004112687, WO-2006135978, WO- 2018145148, and WO-2009018609. [00244] In some embodiments, the compounds disclosed herein are used in combination with cell therapy, such as allogeneic natural killer cells, BM-Allo.MSC, CAStem, IL-15-NK cells, NKG2D- CAR-NK cells, ACE2 CAR-NK cells, partially HLA-matched Virus Specific T cells (VSTs), RAPA-501, or SARS-CoV-2 Specific T Cells. [00245] It is also possible to combine any compound of the invention with one or more additional active therapeutic agents in a unitary dosage form for simultaneous or sequential administration to a patient. The combination therapy may be administered as a simultaneous or sequential regimen. When administered sequentially, the combination may be administered in two or more administrations. [00246] Co-administration of a compound of the invention with one or more other active therapeutic agents generally refers to simultaneous or sequential administration of a compound of the invention and one or more other active therapeutic agents, such that therapeutically effective amounts of the compound of the invention and one or more other active therapeutic agents are both present in the body of the patient. [00247] Co-administration includes administration of unit dosages of the compounds of the invention before or after administration of unit dosages of one or more other active therapeutic agents, for example, administration of the compounds of the invention within seconds, minutes, or hours of the administration of one or more other active therapeutic agents. For example, a unit dose of a compound of the invention can be administered first, followed within seconds or minutes by administration of a unit dose of one or more other active therapeutic agents. Alternatively, a unit dose of one or more other therapeutic agents can be administered first, followed by administration of a unit dose of a compound of the invention within seconds or minutes. In some cases, it may be desirable to administer a unit dose of a compound of the invention first, followed, after a period of hours (e.g., 1-12 hours), by administration of a unit dose of one or more other active therapeutic agents. In other cases, it may be desirable to administer a unit dose of one or more other active therapeutic agents first, followed, after a period of hours ( e.g., 1-12 hours), by administration of a unit dose of a compound of the invention. [00248] The combination therapy may provide "synergy" and "synergistic", i.e. the effect achieved when the active ingredients used together is greater than the sum of the effects that results from using the compounds separately. A synergistic effect may be attained when the active ingredients are: (1) co-formulated and administered or delivered simultaneously in a combined formulation; (2) delivered by alternation or in parallel as separate formulations; or (3) by some other regimen. When delivered in alternation therapy, a synergistic effect may be attained when the compounds are administered or delivered sequentially, e.g. in separate tablets, pills or capsules, or by different injections in separate syringes. In general, during alternation therapy, an effective dosage of each active ingredient is administered sequentially, i.e. serially, whereas in combination therapy, effective dosages of two or more active ingredients are administered together. A synergistic anti-viral effect denotes an antiviral effect which is greater than the predicted purely additive effects of the individual compounds of the combination. [00249] In the various embodiments described herein, the RdRp inhibitor of Formula I, or a pharmaceutically acceptable salt, and/or enantiomer, racemic or scalemic mixture thereof, is a compound selected from Compounds 1-14 in Table 1 shown below. Table 1. Chemical Characterization Data and Assay Results

DETAILED DESCRIPTION OF THE FIGURES [00250] Figure 1. PBMC Concentration of Triphosphates (nM) vs. Time (h) compared to GS-441524. Compound 1 is shown to provide ~10-fold higher DN AUC of GS-443902 (TP) than GS-441524 and TP levels similar to RDV at 24 h. GS-443902 PBMC levels remain > 11.-16 uM at 24 h at 50 mg/kg in cyno NHP, which is 2-2.5x fold better than Cmax obtained from 150 mg RDV via IV over 2 h infusion (Phase 1). Compound 1 is unique when compared to a similar prodrug such as Compound 7 and phosphoramidate of itself (Compound 11) which gave much lower DN AUC of TP. EXAMPLES Abbreviations: [00251] Commonly used abbreviations include: acetyl (Ac), azo-bis-isobutyrylnitrile (AIBN), atmospheres (Atm), 9-borabicyclo[3.3.1]nonane (9-BBN or BBN), tert- butoxycarbonyl (Boc), di-tert-butyl pyrocarbonate or boc anhydride (BOC ₂ O), benzyl (Bn), butyl (Bu), Chemical Abstracts Registration Number (CASRN), benzyloxycarbonyl (CBZ or Z), carbonyl diimidazole (CDI), 1,4-diazabicyclo[2.2.2]octane (DABCO), diethylaminosulfur trifluoride (DAST), dibenzylideneacetone (dba), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), N,N'-dicyclohexylcarbodiimide (DCC), 1,2- dichloroethane (DCE), dichloromethane (DCM), diethyl azodicarboxylate (DEAD), di-iso- propylazodicarboxylate (DIAD), di-iso-butylaluminumhydride (DIBAL or DIBAL-H), 1,3- Diisopropylcarbodiimide (DIC), di-iso-propylethylamine (DIPEA), N,N-dimethyl acetamide (DMA), 4-N,N-dimethylaminopyridine (DMAP), N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,1'-bis-(diphenylphosphino)ethane (dppe), 1,1'-bis- (diphenylphosphino)ferrocene (dppf), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), ethyl (Et), ethyl acetate (EtOAc), ethanol (EtOH), 2-ethoxy-2H- quinoline-1-carboxylic acid ethyl ester (EEDQ), diethyl ether (Et2O), O-(7-azabenzotriazole- 1-yl)-N, N,N’N’-tetramethyluronium hexafluorophosphate acetic acid (HATU), acetic acid (HOAc), 1-N-hydroxybenzotriazole (HOBt), high pressure liquid chromatography (HPLC), iso-propanol (IPA), lithium hexamethyl disilazane (LiHMDS), methanol (MeOH), melting point (mp), MeSO ₂ - (mesyl or Ms), , methyl (Me), acetonitrile (MeCN), m-chloroperbenzoic acid (MCPBA), mass spectrum (ms), methyl t-butyl ether (MTBE), N-bromosuccinimide (NBS), N-carboxyanhydride (NCA), N-chlorosuccinimide (NCS), N-methylmorpholine (NMM), N-methylpyrrolidone (NMP), pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), phenyl (Ph), propyl (Pr), iso-propyl (i-Pr), pounds per square inch (psi), pyridine (pyr), room temperature (rt or RT), tert-butyldimethylsilyl or t-BuMe ₂ Si (TBDMS), triethylamine (TEA or Et ₃ N), 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), triflate or CF ₃ SO ₂ - (Tf), trifluoroacetic acid (TFA), 1,1'-bis-2,2,6,6-tetramethylheptane-2,6-dione (TMHD), O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU), thin layer chromatography (TLC), tetrahydrofuran (THF), trimethylsilyl or Me ₃ Si (TMS), p- toluenesulfonic acid monohydrate (TsOH or pTsOH), 4-Me-C ₆ H ₄ SO ₂ - or tosyl (Ts), N- urethane-N-carboxyanhydride (UNCA),. Conventional nomenclature including the prefixes normal (n), iso (i-), secondary (sec-), tertiary (tert-) and neo have their customary meaning when used with an alkyl moiety. (J. Rigaudy and D. P. Klesney, Nomenclature in Organic Chemistry, IUPAC 1979 Pergamon Press, Oxford.). [00252] Additional embodiments of the disclosure reside in specific examples and data described in more detail herein. [00253] Example 1. ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)- 15-cyano-2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclot etradecin-13-yl)methyl 2- phenylacetate (compound 1) [00254] Step 1. (3aR,4R,6R,6aR)-4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl) -6- (hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol e-4-carbonitrile [00255] To (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3 ,4-dihydroxy-5- (hydroxymethyl)tetrahydrofuran-2-carbonitrile (5 g, 17.17 mmol) dissolved in acetone (50 mL) was added p-TsOH·H ₂ O (4.90 g, 25.75 mmol) followed by 2,2-dimethoxy propane (5.28 mL, 42.92 mmol) at 0°C and the resultant solution was stirred at room temperature for 12 h. After completion of reaction (TLC and LCMS), the volatiles were evaporated in vacuo. The residue was basified by adding sat. NaHCO ₃ solution to adjust the pH to 8-9. The precipitated solid was filtered and dried in vacuo to afford (3aR,4R,6R,6aR)-4-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-6-(hydroxymethyl)-2,2-dimethyltetrahy drofuro[3,4-d][1,3]dioxole-4- carbonitrile (5.0 g, 87%) as white solid. Rf = 0.4 (TLC: 10% MeOH in DCM). [00256] Step 2. ((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl )-6-cyano- 2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-phenylacetate [00257] To (3aR,4R,6R,6aR)-4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl) -6- (hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol e-4-carbonitrile (8 g, 24.14 mmol) and phenyl acetic acid 4 (3.62 g, 26.56 mmol) dissolved in acetonitrile (160 mL) and DMF (40 mL) was added DCC (5.98 g, 28.97 mmol) followed by DMAP (0.29 g, 2.41 mmol) at 0 ^o C and the reaction mixture was stirred at room temperature for 16 h. After completion of reaction (TLC and LCMS), the reaction mixture was quenched by adding H ₂ O (50 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layer was dried over MgSO ₄ and evaporated in vacuo. The crude residue was purified by flash chromatography using 230-400 mesh Silica gel, gradient 0-100% EtOAc in petroleum ether to afford ((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl )-6-cyano-2,2- dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-phenylacetate (7.5 g, 82%) as off- white solid. Rf = 0.45 (TLC: 70% EtOAc in petroleum ether). [00258] Step 3. ((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)- 5-cyano-3,4- dihydroxytetrahydrofuran-2-yl)methyl 2-phenylacetate [00259] To ((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl )-6-cyano-2,2- dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-phenylacetate (14.9 g, 33.15 mmol) was added TFA (59.6 mL) and H ₂ O (29.8 mL) at 0 ^o C and the resulting reaction mixture was stirred at room temperature for 4 h. After completion of reaction (TLC and LCMS), the volatiles were evaporated in vacuo. The residue was basified by adding sat. NaHCO ₃ solution to adjust the pH to 8-9. The precipitated solid was filtered and dried in vacuo. The crude residue was purified by flash chromatography using 230-400 mesh Silica gel, gradient 0-10% MeOH in DCM to afford ((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)- 5- cyano-3,4-dihydroxytetrahydrofuran-2-yl)methyl 2-phenylacetate (10 g, 73%) as off-white solid. Rf = 0.2 (TLC: 5% MeOH in DCM). [00260] Step 4. (2R,3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2 -cyano-5-((2- phenylacetoxy)methyl)tetrahydrofuran-3,4-diyl bis(hex-5-enoate) [00261] To ((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)- 5-cyano-3,4- dihydroxytetrahydrofuran-2-yl)methyl 2-phenylacetate (5.0 g, 12.21 mmol) and hex-5-enoic acid 7 (3.19 mL, 26.87 mmol) dissolved in acetonitrile (100 mL) and DMF (25 mL) was added DCC (6.30 g, 30.53 mmol) followed by DMAP (0.298 g, 2.44 mmol) at 0 ^o C and the reaction mixture was stirred at room temperature for 16 h. After completion of reaction (TLC and LCMS), the reaction mixture was quenched by adding H ₂ O (50 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layer was dried over MgSO ₄ and evaporated in vacuo. The crude residue was purified by flash chromatography using 230-400 mesh Silica gel, gradient 0-100% EtOAc in petroleum ether to afford (2R,3R,4R,5R)-2-(4- aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-cyano-5-((2-phenyl acetoxy)methyl)tetrahydrofuran- 3,4-diyl bis(hex-5-enoate) (4.8 g, 65%) as pale yellow oil. Rf = 0.3 (TLC: 70% EtOAc in petroleum ether). [00262] Step 5. ((12aR,13R,15R,15aR,Z)-15-(4-aminopyrrolo[2,1-f][1,2,4]triaz in-7-yl)-15- cyano-2,11-dioxo-2,3,4,5,8,9,10,11,12a,13,15,15a-dodecahydro furo[3,4- b][1,4]dioxacyclotetradecin-13-yl)methyl 2-phenylacetate (compound 2) [00263] To (2R,3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2 -cyano-5-((2- phenylacetoxy)methyl)tetrahydrofuran-3,4-diyl bis(hex-5-enoate) (2.0 g, 3.32 mmol) was added CHCl ₃ (1000 mL) and the solution was degassed with Ar for 30 min. The solution was further degassed 3 times by FPT (freeze-pump-thaw) cycles. To the solution was added Grubbs’ second generation catalyst (0.282 g, 0.332 mmol) and the reaction mixture was stirred at 50 ^o C for 12 h. After completion of reaction (TLC and LCMS), volatiles were evaporated in vacuo. The crude residue was purified by column chromatography, using 230- 400 mesh Silica gel, gradient 0-50% EtOAc in petroleum ether to afford ((12aR,13R,15R,15aR,Z)-15-(4-aminopyrrolo[2,1-f][1,2,4]triaz in-7-yl)-15-cyano-2,11-dioxo- 2,3,4,5,8,9,10,11,12a,13,15,15a-dodecahydrofuro[3,4-b][1,4]d ioxacyclotetradecin-13- yl)methyl 2-phenylacetate (0.6 g, 31%) as off-white solid. Rf = 0.5 (TLC: 70% EtOAc in petroleum ether). [00264] Step 6. ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-15- cyano-2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetr adecin-13-yl)methyl 2- phenylacetate [00265] In a Steel-bomb pressure reactor, to ((12aR,13R,15R,15aR,Z)-15-(4- aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-15-cyano-2,11-dioxo- 2,3,4,5,8,9,10,11,12a,13,15,15a- dodecahydrofuro[3,4-b][1,4]dioxacyclotetradecin-13-yl)methyl 2-phenylacetate (1.2 g, 2.09 mmol) dissolved in EtOAc (25 mL) was added Pd/C (50% wet basis; 0.120 g, 10% wt/wt) and the reaction mixture was stirred under H ₂ atmosphere (100 psi) at room temperature for 12 h. After completion of reaction (TLC and LCMS), the reaction mixture was filtered through celite and washed with EtOAc (25 mL) and filtrate was evaporated in vacuo. The crude residue was purified by column chromatography, using 230-400 mesh Silica gel, gradient 0-80% EtOAc in petroleum ether followed by RP-Prep HPLC to afford ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-15-cyano-2,11- dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecin-13-y l)methyl 2-phenylacetate(0.941 g, 53%) as off-white solid. Rf = 0.45 (TLC: 70% EtOAc in petroleum ether). LC MS m/z = 576.47 (M+1) ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.03-7.93 (m, 3H), 7.29-7.19 (m, 5H), 6.94 (d, J = 4.4 Hz, 1H), 6.80 (d, J = 4.4 Hz, 1H), 6.12 (d, J = 6.0 Hz, 1H), 5.47 (t, J = 4.0 Hz, 1H), 4.60 (q, J = 4.0 Hz, 1H), 4.41 (dd, J = 12.4, 3.6 Hz, 1H), 4.27 (dd, J = 12.4, 4.8 Hz, 1H), 3.70-3.60 (m, 2H), 2.67-2.33 (m, 4H), 1.61 (bs, 4H), 1.33-1.23 (m, 8H). [00266] Compound 4-7 were prepared similarly according to the above route. [00267] Example 2. (12aR,13R,15R,15aR)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazin- 7-yl)- 15-(hydroxymethyl)-2,11-dioxotetradecahydrofuro[3,4-b][1,4]d ioxacyclotetradecine-13- carbonitrile (compound 3)

[00268] Step 1. (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5 -(((tert- butyldiphenylsilyl)oxy)methyl)-3,4-dihydroxytetrahydrofuran- 2-carbonitrile [00269] To a stirred solution of (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7- yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carboni trile (5 g, 17.17 mmol) in DMF (50 mL) was added Imidazole (8.18 g, 120.16 mmol) followed by TBDPSCl (5.78 mL, 20.60 mmol) at 0°C and then resultant solution was stirred at room temperature for 16 h. After completion of reaction, the reaction mixture was poured in to ice-cold water, solid was precipitated, collected by filtration, dried to get 8 g of (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-5-(((tert-butyldiphenylsilyl)oxy)meth yl)-3,4-dihydroxytetrahydrofuran- 2-carbonitrile as an off white solid. [TLC system: EtOAc: pet-ether (7:3); Rf: 0.6]. [00270] Step 2. (2R,3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5 -(((tert- butyldiphenylsilyl)oxy)methyl)-2-cyanotetrahydrofuran-3,4-di yl bis(hex-5-enoate) [00271] To a solution of (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5 - (((tert-butyldiphenylsilyl)oxy)methyl)-3,4-dihydroxytetrahyd rofuran-2-carbonitrile (3) (3.0 g, 5.66 mmol) and hex-5-enoic acid (1.42 g, 12.46 mmol) in ACN (60 mL), DMF( 15 mL) was added DCC (2.92 g, 14.16 mmol) followed by DMAP (139 mg, 1.13 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 16 h. After completion of reaction, the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layer was dried over MgSO ₄ and concentrated under reduced pressure. The crude compound was purified by column chromatography (240 - 400 mesh, 60 – 70 % EtOAc - Petroleum ether as an eluent) to get 2.3 g of (2R,3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5 -(((tert- butyldiphenylsilyl)oxy)methyl)-2-cyanotetrahydrofuran-3,4-di yl bis(hex-5-enoate) as an off white solid. [TLC system: EtOAc; Rf value: 0.7]. [00272] Step 3. (12aR,13R,15R,15aR,Z)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazi n-7-yl)-15- (((tert-butyldiphenylsilyl)oxy)methyl)-2,11-dioxo-2,3,4,5,8, 9,10,11,12a,13,15,15a- dodecahydrofuro[3,4-b][1,4]dioxacyclotetradecine-13-carbonit rile [00273] To a solution of (2R,3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5 - (((tert-butyldiphenylsilyl)oxy)methyl)-2-cyanotetrahydrofura n-3,4-diyl bis(hex-5-enoate) (0.5 g, 0.73 mmol) in chloroform (150 mL) and the reaction mixture was degassed with Argon for 10 min. Then added Grubbs’ catalyst 2 ^nd generation (0.06 g, 0.85 mmol) at room temperature. The reaction mixture was heated to 50 °C, stirred for 16 h. After completion of reaction by TLC, reaction mixture was filtered through celite pad. The filtrate was collected and concentrated under reduced pressure. The crude compound was purified by column chromatography (240 - 400 mesh, 60 – 70 % EtOAc - Petroleum ether as an eluent) to get 0.22 g of (12aR,13R,15R,15aR,Z)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazi n-7-yl)-15-(((tert- butyldiphenylsilyl)oxy)methyl)-2,11-dioxo-2,3,4,5,8,9,10,11, 12a,13,15,15a- dodecahydrofuro[3,4-b][1,4]dioxacyclotetradecine-13-carbonit rile as an off white solid. [TLC system: EtOAc:Pet-ether (7:3); Rf value: 0.5]. [00274] Step 4. (12aR,13R,15R,15aR)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazin- 7-yl)-15- (((tert-butyldiphenylsilyl)oxy)methyl)-2,11-dioxotetradecahy drofuro[3,4- b][1,4]dioxacyclotetradecine-13-carbonitrile [00275] To a stirred solution of (12aR,13R,15R,15aR,Z)-13-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-15-(((tert-butyldiphenylsilyl)oxy)met hyl)-2,11-dioxo- 2,3,4,5,8,9,10,11,12a,13,15,15a-dodecahydrofuro[3,4-b][1,4]d ioxacyclotetradecine-13- carbonitrile (0.22 g, 0.70 mmol), in MeOH (2 mL) was added 10% Palladium on charcoal (50% wet) (0.02 g) at rt. The resultant reaction mixture was stirred at rt under Hydrogen atmosphere with 100 psi pressure for 16 h. The progress of the reaction was monitored by TLC. After completion of starting material, reaction mixture was filtered through celite pad. The filtrate was collected and concentrated under reduced pressure. The crude compound was purified by column chromatography (240 - 400 mesh, 60 – 70 % EtOAc - Petroleum ether as an eluent) to get 0.13 g of (12aR,13R,15R,15aR)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazin- 7- yl)-15-(((tert-butyldiphenylsilyl)oxy)methyl)-2,11-dioxotetr adecahydrofuro[3,4- b][1,4]dioxacyclotetradecine-13-carbonitrile as an off white solid [TLC system: EtOAc:Pet- ether (7:3); Rf value: 0.4]. [00276] Step 5. (12aR,13R,15R,15aR)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazin- 7-yl)-15- (hydroxymethyl)-2,11-dioxotetradecahydrofuro[3,4-b][1,4]diox acyclotetradecine-13- carbonitrile [00277] To a stirred solution of (12aR,13R,15R,15aR)-13-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-15-(((tert-butyldiphenylsilyl)oxy)met hyl)-2,11- dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecine-13- carbonitrile (0.13 g, 0.69 mmol) in MeOH (1.3 mL) was added NH ₄ F(0.07 g, 0.04 mmol) at 0°C and then resultant solution was stirred at RT for 16 h. After completion of reaction the reaction mixture was quenched by water and extracted with ethyl acetate (2 × 100 mL). The combined organic layer was washed with brine solution (50 mL), dried over MgSO ₄ filtered and evaporated under reduced pressure. The crude compound was purified by column chromatography (240 - 400 mesh, 80 – 90 % EtOAc - Petroleum ether as an eluent) to get 0.0216 g of (12aR,13R,15R,15aR)-13-(4-aminopyrrolo[2,1-f][1,2,4]triazin- 7-yl)-15-(hydroxymethyl)- 2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacyclotetradecin e-13-carbonitrile as an white solid. [TLC system: 100% EtOAc; Rf value: 0.3]. LCMS m/z = 458.39 (M+1); 1H NMR (400 MHz, DMSO-d ₆ ): δ 8.01 (brs,1H), 7.94 (s, 2H), 6.92 (d, J = 4.8 Hz 1H), 6.79 (d, J = 4.4 Hz 1H), 5.97 (d, J = 6.0 Hz, 1H), 5.43 (q, J = 2.8 Hz, 1H), 5.14 (t, J = 5.6 Hz, 1H), 4.37 (q, J = 3.2 Hz, 1H), 3.62 (q, J = 3.2 Hz, 2H), 2.59-2.55 (m, 2H), 2.41- 2.33 (s, 2H), 1.67-1.60 (m, 4H),1.33-1.26 (m, 8H). [00278] Compound 12 was prepared similarly according to the above route. [00279] Example 3. ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)- 15-cyano-2,11-dioxooctahydrofuro[3,4-m][1,3,10,12]tetraoxa[6 ,7]dithiacyclotetradecin-13- yl)methyl 2-phenylacetate (compound 8)

[00280] Step 1. disulfanediylbis(ethane-2,1-diyl) bis(4-nitrophenyl) bis(carbonate) [00281] To a solution of 2,2'-disulfanediylbis(ethan-1-ol) (5.0 g, 32.47 mmol) in DCM (150 mL) was added 4-nitrophenyl carbonochloridate 2 (16.3 g, 81.16 mmol) and Pyridine (12.58 mL, 162.35 mmol) at -20°C and the resultant mixture was stirred at RT for 16 h. After completion, the reaction mixture was diluted with water (100 mL), extracted with DCM (2 x 200 mL) dried over anhydrous Na ₂ SO ₄ and concentrated under reduced pressure. The obtained crude residue was then purified by column chromatography over silica gel (230-400 mesh) using 10-15% EtOAc in petroleum ether to afford disulfanediylbis(ethane-2,1-diyl) bis(4-nitrophenyl) bis(carbonate) (3 g) as yellow solid. TLC system: EtOAc: petroleum ether (2:8); Rf: 0.6. [00282] Step 2. ((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triazin -7-yl)-15- cyano-2,11-dioxooctahydrofuro[3,4-m][1,3,10,12]tetraoxa[6,7] dithiacyclotetradecin-13- yl)methyl 2-phenylacetate [00283] To a stirred solution of ((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7- yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methyl 2-phenylacetate 4 (250 mg, 0.611 mmol) in ACN (7.5 mL) was added disulfanediylbis(ethane-2,1-diyl) bis(4-nitrophenyl) bis(carbonate) (296 mg, 0.611 mmol), and t-BuOK (206 mg, 1.833 mmol) at 0 °C, the resultant mixture was stirred at rt for 16 h. After completion, the reaction mixture was diluted with ice cold water (100 mL) and extracted with ethyl acetate (2 x 200 mL) organic layer was wash with brine (3 x 400) dried over anhydrous Na ₂ SO ₄ and concentrated to give crude. The obtained crude residue was purified by reverse phase Prep-HPLC using following conditions: Column/dimensions: X SELECT -C18 (19*250, 5um) Mobile phase A: 10mM Ammonium Bicarbonate in water Mobile Phase B: Acetonitrile Gradient (Time/%B): 0/25,1/25,9/65,14/65,14.05/98,18/98,18.05/25,20.5/25 Flow rate: 18 ml/min. Solubility: ACN/THF/water. That desired fraction was lyophilized to afford ((12aR,13R,15R,15aR)-15- (4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-15-cyano-2,11-dio xooctahydrofuro[3,4- m][1,3,10,12]tetraoxa[6,7]dithiacyclotetradecin-13-yl)methyl 2-phenylacetate (13 mg) as an off-white solid. TLC system: EtOAc:petroleum ether (10:0); Rf: 0.2. LC MS m/z = 616.39 (M+1) 1H NMR (400 MHz, DMSO-d ₆ ) δ 8.08-7.96 (m, 3H), 7.30-7.20 (m, 5H), 6.96 (d, J = 4.4 Hz, 1H), 6.81 (d, J = 4.8 Hz, 1H), 6.08 (d, J = 6 Hz, 1H), 5.40 (t, J = 5.2 Hz, 1H), 4.69-4.62 (m, 2H), 4.51-4.43 (m, 2H), 4.35-4.26 (m, 3H), 3.70 (q, J = 4.8 Hz, 2H), 3.35 (bs, 1H), 3.12-3.15 (m, 1H), 3.02-2.96 (m, 2H). [00284] Example 4.2-ethylbutyl ((((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-15-cyano-2,11-dioxotetradecahydrofuro [3,4- b][1,4]dioxacyclotetradecin-13-yl)methoxy)(phenoxy)phosphory l)-L-alaninate (compound 11)

[00285] Step 1: (2R,3R,4R,5R)-5-{4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl}-5 -cyano-2- ({[(S)-[(2S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl]amino(phenox y)phosphoryl]oxy}methyl)-4- (hex-5-enoyloxy)oxolan-3-yl hex-5-enoate [00286] To a stirred mixture of 5-hexenoic acid (2.08 g, 18.2 mmol, 2.2 eq), EDCI (3.98 g, 20.7 mmol, 2.5 eq) and DMAP (0.10 g, 0.8 mmol, 0.1 eq) in DCM (100 mL) were added 2- ethylbutyl (2S)-2-{[(S)-[(2R,3S,4R,5R)-5-{4-aminopyrrolo[2,1-f][1,2,4]t riazin-7-yl}-5-cyano- 3,4-dihydroxyoxolan-2-yl]methoxy(phenoxy)phosphoryl]amino}pr opanoate (5 g, 8.3 mmol, 1.0 eq) in portions at 0°C under nitrogen atmosphere. The resulting mixture was stirred for additional 2h at room temperature. The reaction was quenched with water (20 mL) at room temperature and then extracted with DCM (2 x 50mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with Petroleum ether:ethyl acetate (6:4) to afford (2R,3R,4R,5R)-5- {4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl}-5-cyano-2-({[(S)- [(2S)-1-(2-ethylbutoxy)-1- oxopropan-2-yl]amino(phenoxy)phosphoryl]oxy}methyl)-4-(hex-5 -enoyloxy)oxolan-3-yl hex-5-enoate as a white solid (5 g, 75%). LC/MS m/z = 795 (M+1). [00287] Step 2: 2-ethylbutyl ((((12aR,13R,15R,15aR,Z)-15-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-15-cyano-2,11-dioxo-2,3,4,5,8,9,10,11 ,12a,13,15,15a- dodecahydrofuro[3,4-b][1,4]dioxacyclotetradecin-13-yl)methox y)(phenoxy)phosphoryl)- L-alaninate (compound 10) [00288] To a stirred mixture of (2R,3R,4R,5R)-5-{4-aminopyrrolo[2,1-f][1,2,4]triazin-7- yl}-5-cyano-2-({[(S)-[(2S)-1-(2-ethylbutoxy)-1-oxopropan-2- yl]amino(phenoxy)phosphoryl]oxy}methyl)-4-(hex-5-enoyloxy)ox olan-3-yl hex-5-enoate (5 g, 6.3 mmol, 1.0 eq) in DCE (2500 mL) were added Grubbs’ 2 ^nd (0.53 g, 0.63 mmol, 0.1 eq) at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80°C. After the reaction was completed, the mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, ACN in Water (0.1% NH ₃ ·H ₂ O), 10% to 50% gradient in 20 min; detector, UV 254 nm. to afford 2-ethylbutyl ((((12aR,13R,15R,15aR,Z)-15-(4-aminopyrrolo[2,1-f][1,2,4]tri azin-7-yl)-15-cyano-2,11- dioxo-2,3,4,5,8,9,10,11,12a,13,15,15a-dodecahydrofuro[3,4-b] [1,4]dioxacyclotetradecin-13- yl)methoxy)(phenoxy)phosphoryl)-L-alaninate as a white solid (3 g, 62%). LC/MS m/z = 767 (M+1); 1H NMR (400 MHz, DMSO-d6): 8.06 – 7.92 (m, 3H), 7.30 – 7.26 (m, 2H), 7.15 – 7.10 (m, 3H), 6.90 – 6.90 (m, 1H), 6.78 – 6.77 (m, 1H), 6.13 – 6.04 (m, 1H), 5.94 – 5.92 (m, 1H), 5.51 – 5.33 (m, 3H), 4.54 (s, 1H), 4.36 – 4.18 (m, 2H), 3.97 – 3.96 (m, 1H), 3.95 – 3.93 (m, 1H), 3.87 – 3.86 (m, 1H), 2.51 – 2.41 (m, 3H), 2.11 – 2.08 (m, 3H), 1.99 – 1.78 (m, 4H), 1.66 – 1.45 (m, 3H), 1.28 – 1.22 (m, 4H), 1.18 – 1.14(m, 3H), 0.82 – 0.78 (m, 6H). [00289] Step 3: 2-ethylbutyl ((((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-15-cyano-2,11-dioxotetradecahydrofuro [3,4- b][1,4]dioxacyclotetradecin-13-yl)methoxy)(phenoxy)phosphory l)-L-alaninate (compound 11) [00290] To a solution of 2-ethylbutyl ((((12aR,13R,15R,15aR,Z)-15-(4-aminopyrrolo[2,1- f][1,2,4]triazin-7-yl)-15-cyano-2,11-dioxo-2,3,4,5,8,9,10,11 ,12a,13,15,15a- dodecahydrofuro[3,4-b][1,4]dioxacyclotetradecin-13-yl)methox y)(phenoxy)phosphoryl)-L- alaninate (INT-2; 3 g, 3.9 mmol, 1 eq) in 1,4-dioxane (30 mL) was added Pd/C (10%wt, 300mg) in a pressure tank. The mixture was hydrogenated at 50℃ under 10 psi of hydrogen pressure for overnight. After the reaction was completed, the mixture was filtered through a Celite pad and concentrated under reduced pressure. The residue was purified by reversed- phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, ACN in Water (0.1% NH ₃ ·H ₂ O), 10% to 50% gradient in 20 min; detector, UV 254 nm. to afford 2-ethylbutyl ((((12aR,13R,15R,15aR)-15-(4-aminopyrrolo[2,1-f][1,2,4]triaz in-7- yl)-15-cyano-2,11-dioxotetradecahydrofuro[3,4-b][1,4]dioxacy clotetradecin-13- yl)methoxy)(phenoxy)phosphoryl)-L-alaninate as a white solid (1.25 g, 41%). LC/MS m/z = 769 (M+1); 1H NMR (400 MHz, DMSO-d ₆ ): 8.06 – 7.91 (m, 3H), 7.30 – 7.26 (m, 2H), 7.15 – 7.10 (m, 3H), 6.90 – 6.89 (m, 1H), 6.74 – 6.73 (m, 1H), 6.06 – 5.99 (m, 2H), 5.46 – 5.43 (m, 1H), 4.57 (s, 1H), 4.44 – 4.22 (m, 2H), 3.95 – 3.93 (m, 1H), 3.88 – 3.86 (m, 1H), 3.85 – 3.75 (m, 1H), 2.56 – 2.50 (m, 2H), 2.50 – 2.37 (m, 2H), 1.61 – 1.59 (m, 4H), 1.43 – 1.41 (m, 1H), 1.32 – 1.22 (m, 12H), 1.18 – 1.16 (m, 3H), 0.82 – 0.78 (m, 6H). [00291] Compound 9 was prepared similarly. Pharmacokinetic Data [00292] Figure 1 shows the PBMC concentration of triphosphates over time compared to GS-441524. Compound 1 is shown to provide ~10-fold higher DN AUC of GS-443902 (TP) than GS-441524 and TP levels similar to RDV at 24 h. GS-443902 PBMC levels remain > 11-16 uM at 24 h at 50 mg/kg in cyno NHP, which is 2-2.5x fold better than Cmax obtained from 150 mg RDV via IV over 2 h infusion (Phase 1). Compound 1 is unique when compared to a similar prodrug such as Compound 7 and phosphoramidate of itself (Compound 11) which gave much lower DN AUC of TP. [00293] The formulation of sacchrinate salt of compound 1: 100 mg/mL suspension (0.2% Methyl cellulose in 50 mM 6.8pH Phosphate buffer, pH = 5.23); suspension was found to be stable at accelerated conditions after 2 weeks.10 mg/mL solution (20% Transcutol, 10% Kolliphor-EL in 50 mM 6.8pH Phosphate buffer, pH = 7.3); solution was found to be stable stable at 2-8°C & RT after 2 weeks. [00294] Table 2 below provides the protocols followed and key data for Figure 1:

Table 2. [00295] The foregoing disclosure has been described in some detail by way of illustration and example, for purposes of clarity and understanding. It will be obvious to one of skill in the art that changes and modifications may be practiced within the scope of the appended claims. Therefore, it is to be understood that the above description is intended to be illustrative and not restrictive. The scope of the disclosure should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the following appended claims, along with the full scope of equivalents to which such claims are entitled. [00296] This application refers to various issued patents, published patent applications, journal articles, and other publications, each of which are incorporated herein by reference.