Hepatitis C virus NS5B RNA-dependent RNA polymerase (HCV NS5B RdRp) (HCV NS5B RdRp)

The Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) is a 66 kDa membrane-associated enzyme essential for the replication of the HCV viral genome (UniProt: P26663). It catalyzes the synthesis of a negative-strand RNA intermediate from the positive-strand genomic RNA, which then serves as a template for the production of new viral genomes (PubMed: 10562230). Structurally, NS5B features a characteristic right-hand fold with fingers, palm, and thumb domains that facilitate the binding of the RNA template and nucleotide triphosphates (PubMed: 10562230). Because humans lack a homologous RNA-dependent RNA polymerase, NS5B is a highly selective and effective target for direct-acting antiviral (DAA) drugs (NIH: NBK548557). These drugs include nucleoside/nucleotide inhibitors (NIs) like sofosbuvir, which act as chain terminators, and non-nucleoside inhibitors (NNIs) like dasabuvir, which bind to allosteric sites to prevent the conformational changes required for polymerization (PubMed: 24128701). Clinical use of NS5B inhibitors has revolutionized the treatment of chronic hepatitis C, leading to high rates of sustained virologic response and reducing the risk of liver cirrhosis and hepatocellular carcinoma (PubMed: 25514806).

Other names

NS5BNon-structural protein 5BRNA-directed RNA polymeraseHCV RdRp

Nucleoside/nucleotide analogs act as chain terminators; Non-nucleoside inhibitors act as allosteric inhibitors.