Modified fluorinated nucleoside analogues

Abstract

The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

1 - 129 . (canceled) 
     
     
         130 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L) or its pharmaceutically acceptable salt of the structure: 
       
         
           
           
               
               
           
         
         wherein the base is a pyrrolopyrimidine base represented by the following formula: 
       
       
         
           
           
               
               
           
         
         X is O, S, CH 2 , Se, NH, N-alkyl, CHW (R, S, or racemic), C(W) 2 , wherein W is F, Cl, Br, or I; 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate; R 2  is H or phosphate; R 1  and R 2  or R 7  can also be linked with cyclic phosphate group; 
         R 2  and R 2  are independently H, C 1-4  alkyl, C 1-4  alkenyl, C 1-4  alkynyl, vinyl, N 3 , CN, Cl, Br, F, I, NO2, C(O)O(C 1-4  alkyl), C(O)O(C 1-4  alkyl), C(O)O(C 1-4  alkynyl), C(O)O(C 1-4  alkenyl), O(C 1-4  acyl), O(C 1-4  alkyl), O(C 1-4  alkenyl), S(C 1-4  acyl), S(C 1-4  alkyl), S(C 1-4  alkynyl), S(C 1-4  alkenyl), SO(C 1-4  acyl), SO(C 1-4  alkyl), SO(C 1-4  alkynyl), SO(C 1-4  alkenyl), SO 2 (C 1-4  acyl), SO 2 (C 1-4  alkyl), SO 2 (C 1-4  alkynyl), SO 2 (C 1-4  alkenyl), O 3 S(C 1-4  acyl), O 3 S(C 1-4  alkyl), O 3 S(C 1-4  alkenyl), NH 2 , NH(C 1-4  alkyl), NH(C 1-4  alkenyl), NH(C 1-4  alkynyl), NH(C 1-4  acyl), N(C 1-4  alkyl) 2 , N(C 1-18  acyl) 2 , wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N 3 , CN, one to three halogen (Cl, Br, F, I), NO 2 , C(O)O(C 1-4  alkyl), C(O)O(C 1-4  alkyl), C(O)O(C 1-4  alkynyl), C(O)O(C 1-4  alkenyl), O(C 1-4  acyl), O(C 1-4  alkyl), O(C 1-4  alkenyl), S(C 1-4  acyl), S(C 1-4  alkyl), S(C 1-4  alkynyl), S(C 1-4  alkenyl), SO(C 1-4  acyl), SO(C 1-4  alkyl), SO(C 1-4  alkynyl), SO(C 1-4  alkenyl), SO 2 (C 1-4  acyl), SO 2 (C 1-4  alkyl), SO 2 (C 1-4  alkynyl), SO 2 (C 1-4  alkenyl), O 3 S(C 1-4  acyl), O 3 S(C 1-4  alkyl), O 3 S(C 1-4  alkenyl), NH 2 , NH(C 1-4  alkyl), NH(C 1-4  alkenyl), NH(C 1-4  alkynyl), NH(C 1-4  acyl), N(C 1-4  alkyl) 2 , N(C 1-4  acyl) 2 , OR 7 ; R 2  and R 2′  can be linked together to form a vinyl optionally substituted by one or two of N 3 , CN, Cl, Br, F, I, NO 2 ; 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro; 
         R 4  and R 5  are independently H, halogen including F, Cl, Br, I, OH, OR′, SH, SR′, NH 2 , NHR′, NR′ 2 , lower alkyl of C 1 -C 6 , halogenated (F, Cl, Br, I) lower alkyl of C 1 -C 6 , lower alkenyl of C 2 -C 6 , halogenated (F, Cl, Br, I) lower alkenyl of C 2 -C 6 , lower alkynyl of C 2 -C 6  such as C≡CH, halogenated (F, Cl, Br, I) lower alkynyl of C 2 -C 6 , lower alkoxy of C 1 -C 6  such as CH 2 OH and CH 2 CH 2 OH, halogenated (F, Cl, Br, I) lower alkoxy of C 1 -C 6 , lower hydroxyalkyl, CO 2 H, CO 2 R′, CONH 2 , CONHR′, CONR′ 2 , CH═CHCO 2 H, CH═CHCO 2 R′; and 
         R′ is an optionally substituted alkyl of C 1 -C 12 , cycloalkyl, optionally substituted alkynyl of C 2 -C 6 , optionally substituted lower alkenyl of C 2 -C 6  or optionally substituted acyl. 
         when n is 1, then R 4  is ═O. 
         when n is 0, then a double bond exists between position 1 and position 6. 
       
     
     
         131 . The (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) of  claim 130  or its pharmaceutically acceptable salt thereof,
 wherein the Base is represented by the following formula:   
       
         
           
           
               
               
           
         
         when n is 0, then R 4  is NH 2 , R 5  is H and a double bond exists between position 1 and position 6; when n is 1, then R 4  is ═O and R 5  is NH 2 . 
       
     
     
         132 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L) or its pharmaceutically acceptable salt of the structure: 
       
         
           
           
               
               
           
         
         wherein the base is a pyrrolopyrimidine base; 
         X is O, S, CH 2 , Se, NH, N-alkyl, CHW (R, S, or racemic), C(W) 2 , wherein W is F, Cl, Br, or I; 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, allyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate; R 2  is H or phosphate; R 1  and R 2  or R 7  can also be linked with cyclic phosphate group. 
       
     
     
         133 . The (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) of  claim 132  or its pharmaceutically acceptable salt thereof,
 wherein the Base is represented by the following formula:   
       
         
           
           
               
               
           
         
         when n is 0, then R 4  is NH 2 , R 5  is H and a double bond exists between position 1 and position 6; when n is 1, then R 4  is ═O and R 5  is NH 2 . 
       
     
     
         134 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  or R 7  is independently H or phosphate; R 1  and R 7  can also be linked with cyclic phosphate group; and 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro. 
       
     
     
         135 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         136 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate. 
       
     
     
         137 . A (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         138 . A pharmaceutical composition comprising the nucleoside of  claim 130  or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. 
     
     
         139 . A pharmaceutical composition comprising the nucleoside of  claim 131  or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. 
     
     
         140 . A pharmaceutical composition comprising the nucleoside of  claim 132  or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. 
     
     
         141 . A pharmaceutical composition comprising the nucleoside of  claim 133  or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. 
     
     
         142 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L), or its pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier, of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  or R 7  is independently H or phosphate; R 1  and R 7  can also be linked with cyclic phosphate group; and 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro. 
       
     
     
         143 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D or β-L), or its pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         144 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D), or its pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate. 
       
     
     
         145 . A pharmaceutical composition comprising a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D), or its pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         146 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 130  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         147 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 131  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         148 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 132  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         149 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 133  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         150 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  or R 7  is independently H or phosphate; R 1  and R 7  can also be linked with cyclic phosphate group; and 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         151 . A method for the treatment of prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         152 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         153 . A method for the treatment or prophylaxis of Hepatitis C infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         154 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 130  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         155 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 131  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         156 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 132  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         157 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 133  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         158 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  or R 7  is independently H or phosphate; R 1  and R 7  can also be linked with cyclic phosphate group; and 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         159 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         160 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         161 . A method for the treatment or prophylaxis of Rhinovirus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         162 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 130  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         163 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 131  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         164 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 132  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         165 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 133  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         166 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  or R 7  is independently H or phosphate; R 1  and R 7  can also be linked with cyclic phosphate group; and 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         167 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         168 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         169 . A method for the treatment or prophylaxis of Yellow Fever Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         170 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 130  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         171 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 131  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         172 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 132  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         173 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 133  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         174 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipids, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  or R 7  is independently H or phosphate; R 1  and R 7  can also be linked with cyclic phosphate group; and 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         175 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         176 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         177 . A method for the treatment or prophylaxis of West Nile Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         178 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 130  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         179 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 131  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         180 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 132  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         181 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of the nucleoside of  claim 133  or its pharmaceutically acceptable salt optionally in a pharmaceutically acceptable carrier. 
     
     
         182 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 7  are independently H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  or R 7  is independently H or phosphate; R 1  and R 7  can also be linked with cyclic phosphate group; and 
         R 6  is an optionally substituted alkyl (including lower alkyl), cyano (CN), CH 3 , OCH 3 , OCH 2 CH 3 , hydroxy methyl (CH 2 OH), fluoromethyl (CH 2 F), azido (N 3 ), CHCN, CH 2 N 3 , CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , alkyne (optionally substituted), or fluoro. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         183 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         184 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug, H-phosphonate, including stabilized H-phosphonates, acyl, including optionally substituted phenyl and lower acyl, alkyl, including lower alkyl, O-substituted carboxyalkylamino or its peptide derivatives, sulfonate ester, including alkyl or arylalkyl sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted, a lipid, including a phospholipid, an L or D-amino acid (or racemic mixture), a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1  is H or phosphate. 
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         185 . A method for the treatment or prophylaxis of Dengue Virus infection comprising administering to a host an antivirally effective amount of a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside (β-D) or its pharmaceutically acceptable salt thereof of the formula: 
       
         
           
           
               
               
           
         
         optionally in a pharmaceutically acceptable carrier. 
       
     
     
         186 . The method of  claim 146 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         187 . The method of  claim 151 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         188 . The method of  claim 153 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         189 . The method of  claim 154 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         190 . The method of  claim 159 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         191 . The method of  claim 161 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         192 . The method of  claim 162 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and anti sense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         193 . The method of  claim 167 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         194 . The method of  claim 169 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interlekin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         195 . The method of  claim 170 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         196 . The method of  claim 175 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         197 . The method of  claim 177 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         198 . The method of  claim 178 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         199 . The method of  claim 183 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate. 
     
     
         200 . The method of  claim 185 , wherein the antivirally effective amount of (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleoside is administered in combination or alternation with at least one treatment selected from the group consisting of: interferon, including interferon alpha 2a, interferon alpha 2b, a pegylated interferon, interferon beta, interferon gamma, interferon tau and interferon omega; an interleukin, including interleukin 10 and interleukin 12; ribavirin; interferon alpha or pegylated interferon alpha in combination with ribavirin or levovirin; levovirin; a protease inhibitor including NS3 inhibitor, a NS3-4A inhibitor; a helicase inhibitor; a polymerase inhibitor including HCV RNA polymerase and NS5B polymerase inhibitor; gliotoxin; an IRES inhibitor, and antisense oligonucleotide; a thiazolidine derivative; a benzanilide, a ribozyme; another nucleoside, nucleoside prodrug or nucleoside derivative; a 1-amino-alkylcyclohexane; an antioxidant including vitamin E; squalene; amantadine; a bile acid; N-(phosphonoacetyl)-L-aspartic acid; a benzenedicarboxamide; polyadenylic acid; a benzimidazole; thymosin; a beta tubulin inhibitor; a prophylactic vaccine; an immune modulator, an IMPDH inhibitor; silybin-phosphatidylcholine phytosome; and mycophenolate.