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Non-structural protein 5B (NS5B) is an RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) genome. It is an essential viral enzyme responsible for replication of the positive-strand viral RNA and is localized near the endoplasmic reticulum as part of the replication complex. Structurally, NS5B shows a typical right-hand polymerase architecture with finger, palm, and thumb domains, and catalyzes RNA synthesis de novo. Because this function is unique and not present in mammalian cells, NS5B is an attractive and validated target for direct-acting antiviral (DAA) drugs against HCV, with both nucleoside and non-nucleoside inhibitors clinically approved and in development. NS5B also interacts with other HCV proteins and cellular factors, playing roles in viral genome replication, assembly, and possibly morphogenesis[1][2][3][4][5].
Inhibition of RNA-dependent RNA polymerase activity, blocking replication of viral RNA (nucleoside analogues act as chain terminators, non-nucleoside inhibitors bind allosteric sites and inhibit polymerase function)[2][4]
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