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Hepatitis C virus RNA-dependent RNA polymerase (NS5B) is a viral enzyme essential for the replication of the hepatitis C virus genome. NS5B catalyzes the polymerization of ribonucleoside triphosphates using the viral positive-sense RNA strand as a template, enabling viral RNA replication via a de novo synthesis mechanism. NS5B is a well-characterized target for direct-acting antivirals due to its indispensable role in the viral life cycle. Several drugs—mainly nucleotide analogs and non-nucleoside allosteric inhibitors—have been developed or approved to inhibit its activity, leading to effective treatments for hepatitis C virus infection. Mutations in the NS5B gene are associated with resistance to specific polymerase inhibitors, which has therapeutic implications for drug selection and resistance testing.
Nucleotide analog inhibitors: act as chain terminators when incorporated into viral RNA (e.g. sofosbuvir) Non-nucleoside inhibitors: bind allosteric sites on the enzyme, impairing its function (e.g. dasabuvir)
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