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Computational Study on the Drug Resistance Mechanism of HCV NS5B RNA-dependent RNA Polymerase Mutants V494I, V494A, M426A, and M423T to Filibuvir

Huiqun Wang, Chenchen Guo, Bo-Zhen Chen, Mingjuan Ji

Antiviral Res. 2015 Jan;113:79-92.

PMID: 25449363

Abstract:

Filibuvir, a potent non-nucleoside inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp), has shown great promise in phase IIb clinical trial. However, drug resistant mutations towards Filibuvir have been identified. In the present study, the drug resistance mechanism of wild-type (WT) and mutant NS5B polymerases (including V494I, V494A, M426A, and M423T) toward Filibuvir was investigated by molecular modeling methods. The predicted binding free energy of these five complexes is highly consistent with the experimental EC50 values of Filibuvir to the wild-type and mutant NS5B RdRps, V494I

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP877130284 Filibuvir Filibuvir 877130-28-4 Price
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