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

Hepatitis C virus nonstructural protein 5B (NS5B) is a 66-kDa RNA-dependent RNA polymerase essential for the replication of HCV's positive-stranded RNA genome[1][5][6][7]. As a viral enzyme not found in mammalian cells, NS5B is responsible for catalyzing the polymerization of ribonucleoside triphosphates (rNTPs) to synthesize new viral RNA strands, operating via de novo initiation[1][5][6][7]. Its unique structure, often described as a right-hand shape with finger, palm, and thumb subdomains, is critical for its function, and the active site resides in the palm region[1][5][6][8]. NS5B is the molecular target of several direct-acting antivirals (DAAs), including nucleotide inhibitors like sofosbuvir and non-nucleoside inhibitors like dasabuvir, which prevent viral replication and are key in modern HCV therapy[1][2][4][6]. The enzyme's specificity for viral RNA replication and lack of expression in uninfected host cells make it an attractive target with a favorable therapeutic index, though challenges with drug resistance and access to DAAs remain[2][4][6].

Other names

NS5BHCV NS5B polymerasehepatitis C virus RNA-dependent RNA polymeraseHCV polymerasenon-structural protein 5B

Nucleotide analogues (induce RNA chain termination by mimicking rNTPs and being incorporated into RNA); Non-nucleoside allosteric inhibitors (bind allosteric sites, impairing enzyme function); Pyrophosphate analogues (inhibit catalysis at the active site)