Hepatitis C virus non-structural protein 5B (NS5B) RNA-dependent RNA polymerase (NS5B)

The Hepatitis C virus non-structural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) essential for the replication of the HCV genome (UniProt: P26664). It functions as the catalytic core of the viral replication complex, utilizing a positive-sense RNA template to synthesize a negative-sense intermediate, which then serves as a template for new genomic RNA (PubMed: 11581170). Structurally, NS5B features a classic polymerase "right-hand" architecture consisting of fingers, palm, and thumb domains that coordinate the binding of RNA and ribonucleotide triphosphates (rNTPs) (PubMed: 10490630). As an enzyme with no human homolog, NS5B is a primary target for direct-acting antiviral (DAA) therapy, specifically through nucleoside analogs like sofosbuvir that cause chain termination and non-nucleoside inhibitors that bind allosteric sites (PubChem: CID 45375808). These therapies have revolutionized the treatment of chronic hepatitis C, offering high cure rates and reducing the risk of long-term complications such as cirrhosis and hepatocellular carcinoma (StatPearls: NBK448088).

Other names

HCV NS5BRNA-directed RNA polymeraseRdRpNS5B polymeraseNon-structural protein 5B

Nucleoside/nucleotide analogs (NIs) act as alternative substrates for the polymerase, leading to premature RNA chain termination; non-nucleoside inhibitors (NNIs) bind to allosteric sites on the enzyme (thumb or palm domains) to prevent the conformational changes required for the initiation or elongation of RNA synthesis (PubMed: 19131601).