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Overview
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Background
VX-222, a derivative of thiophene-2-carboxylic acid, is a potent non-nucleoside inhibitor (NNI) of the hepatitis C virus (HCV) RNA polymerase, an enzyme regulating RNA synthesis by a de novo-initiated mechanism or by extension from a primed template, that binds to the thumb II allosteric pocket of HCV RNA-dependent RNA polymerase with hydrophobical interactions between the 4-methycyclohexanoyl group of VX-222 and L412, M423 and I482 of thumb II domain. VX-222 exhibits preferential inhibition against primer-dependent RNA synthesis rather than de novo-initiated RNA synthesis with 50% inhibition concentration IC50 values ranging from 0.011 to >5 μM in five different templates of RNA synthesis.
Yi G, Deval J, Fan B, Cai H, Soulard C, Ranjith-Kumar CT, Smith DB, Blatt L, Beigelman L, Kao CC. Biochemical study of the comparative inhibition of hepatitis C virus RNA polymerase by VX-222 and filibuvir. Antimicrob Agents Chemother. 2012 Feb;56(2):830-7. doi: 10.1128/AAC.05438-11. Epub 2011 Dec 5.
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