2′-branched nucleosides and flaviviridae mutation

A method of treating a hepatitis C virus infection in a host, comprising:

• (a) administering an effective amount of a compound of formula III:
• or a pharmaceutically acceptable salt, a stereoisomeric, tautomeric or polymorphic form thereof, wherein:
• Base is uracil;
• R1 is mono-, di- or triphosphate, or a stabilized phosphate;
• R2 is hydrogen;
• R6 is alkyl, CH3, CF3, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R7 is fluorine;
• and
• X is O, S, SO2, or CH2;
• (b) identifying viral resistance to the compound of formula III in the host by detecting an amino acid 282 Ser to Thr mutation in the RNA polymerase region of the hepatitis C virus;
• and
• (c) administering to the host infected with the virus resistant to the compound of formula III, an effective amount of one or more drugs that directly or indirectly induce a mutation in a hepatitis C virus at a location other than nucleotide 8443 (G to C) of the hepatitis C virus genome or amino acid 282 Ser to Thr of the RNA polymerase region of hepatitis C virus.