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

The Hepatitis C virus nonstructural protein 5B (NS5B) is a 66 kDa membrane-associated enzyme that functions as an RNA-dependent RNA polymerase (RdRp), serving as the central catalytic component of the HCV replication complex (UniProt: P26663). It is responsible for the synthesis of the negative-strand RNA template and the subsequent production of new positive-strand viral genomes (PubMed: 11533173). Because RNA-dependent RNA polymerase activity is absent in human cells, NS5B represents a highly specific therapeutic target with a favorable safety profile (NIH: NBK548557). Therapeutic strategies include nucleoside/nucleotide analogs like sofosbuvir, which act as chain terminators, and non-nucleoside inhibitors like dasabuvir, which bind to allosteric sites to inhibit conformational transitions (PubMed: 25514044). Effective inhibition of NS5B is a cornerstone of modern direct-acting antiviral (DAA) regimens, enabling high cure rates for chronic hepatitis C infection.

Other names

HCV RdRpRNA-directed RNA polymeraseNon-structural protein 5BHCV NS5B

Inhibition of viral RNA synthesis through competitive chain termination by nucleotide analogs or allosteric modulation of the polymerase structure by non-nucleoside inhibitors.