Non-structural protein 5B RNA-dependent RNA polymerase of hepatitis C virus (NS5B)

Non-structural protein 5B (NS5B) is a viral RNA-dependent RNA polymerase encoded by hepatitis C virus (HCV). It is essential for replication of the viral RNA genome, catalyzing the synthesis of progeny RNA strands from the viral single-stranded positive-sense RNA template. NS5B exhibits a right-hand-like shape with finger, palm, and thumb subdomains, with a central active site residing in the palm region. The enzyme catalyzes RNA synthesis by a de novo mechanism, first forming a dinucleotide and then processively elongating the nascent RNA chain. Drugs targeting NS5B include both nucleoside/nucleotide analogs and non-nucleoside inhibitors, which disrupt replication and are highly effective in modern direct-acting antiviral therapies for chronic HCV infection. Resistance mutations may limit efficacy of some inhibitors, necessitating combination therapy with agents targeting other viral proteins. NS5B's essential role in HCV replication and its virus-specific nature make it a prime therapeutic target in antiviral drug development.

Other names

NS5BHepatitis C virus nonstructural protein 5BHCV NS5B RNA-dependent RNA polymeraseHCV RdRp

Nucleoside/nucleotide analog inhibitors: Incorporate into growing viral RNA chain, cause chain termination (e.g., Sofosbuvir). Non-nucleoside inhibitors: Bind allosterically, alter polymerase conformation, inhibit activity (e.g., Dasabuvir). Inhibition of RNA polymerization, preventing viral replication.