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

Hepatitis C virus nonstructural protein 5B RNA-directed RNA polymerase (NS5B) is a viral enzyme essential for the replication of the hepatitis C virus (HCV)[1][4][3]. It catalyzes the synthesis of viral RNA by using the viral positive-strand RNA as a template, and is structurally distinct with finger, palm, and thumb domains forming an encircled active site. NS5B initiates RNA synthesis de novo, without a primer, and is absolutely required for viral genome replication[1][3][4]. Its unique features and essential function make it a validated, druggable target for anti-HCV therapies, with several approved drugs or candidates that act as NS5B inhibitors. The inhibition of NS5B effectively halts viral replication and is a central component of modern direct-acting antiviral (DAA) therapies for hepatitis C infection[1][4]. Monitoring of HCV RNA titers is used to assess response to NS5B-targeted treatments. Resistance and combination therapy requirements are primary therapeutic challenges.

Other names

NS5BHepatitis C virus RNA-dependent RNA polymeraseHCV RNA polymerase

Inhibition of RNA-dependent RNA polymerase activity: - Nucleoside/nucleotide analog inhibitors: Act as chain terminators or faulty substrates (e.g., Sofosbuvir) that get incorporated by NS5B, blocking further RNA synthesis[1]. - Non-nucleoside inhibitors: Bind to allosteric sites on NS5B to inhibit polymerase activity by altering enzyme conformation (e.g., Dasabuvir)[1].