RNA-dependent RNA polymerase of Hepatitis C virus (NS5B)

RNA-dependent RNA polymerase of Hepatitis C virus, most commonly known as NS5B, is a viral enzyme essential for the replication of the HCV RNA genome[3][6]. NS5B catalyzes the synthesis of new viral RNA strands using the existing RNA genome as a template, functioning as part of a membrane-associated replication complex within infected cells[1][3][6]. Structurally, NS5B shares a right-hand fold typical of viral polymerases, with specialized "fingers," "palm," and "thumb" domains, and possesses unique structural motifs for RNA template recognition and catalysis[2][4][5]. Its essential role in the HCV life cycle and lack of closely related human homologues make it the major target for antiviral drugs (notably sofosbuvir and dasabuvir), which inhibit polymerase activity by causing premature chain termination or allosteric inhibition[5][6]. Monitoring for resistance-associated variants in NS5B is important in optimizing therapy, and combination regimens are standard to mitigate rapid resistance development[6].

Other names

HCV NS5BHCV RdRpHepatitis C virus nonstructural protein 5B

Nucleoside/nucleotide analogue inhibition (chain termination); Allosteric inhibition of polymerase enzymatic activity