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

Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase is the essential catalytic enzyme responsible for replicating the viral RNA genome (UniProt P26664). It functions by synthesizing a negative-strand RNA intermediate from the positive-strand genomic RNA, which then serves as a template for new viral genomes (PubMed: 11581173). As a key component of the viral replication complex, NS5B is a primary target for direct-acting antiviral (DAA) medications used to treat chronic hepatitis C (NIH: NBK548557). These drugs include nucleoside/nucleotide analogs, such as sofosbuvir, which act as chain terminators, and non-nucleoside inhibitors, such as dasabuvir, which bind to allosteric sites to inhibit enzymatic activity (PubChem CID 45375808). Targeting this enzyme is highly effective because there is no human homolog, minimizing off-target effects while successfully clearing the virus in the majority of patients (PubMed: 24552135).

Other names

NS5B polymeraseHCV RdRpRNA-directed RNA polymeraseNon-structural protein 5BHCV RNA-dependent RNA polymeraseHCV RNA synthesis

Inhibition of viral RNA synthesis through either competitive inhibition and chain termination (nucleoside/nucleotide analogs) or allosteric modulation (non-nucleoside inhibitors) of the NS5B RNA-dependent RNA polymerase, thereby preventing the replication of the HCV genome.