RNA-directed RNA Polymerase NS5B (NS5B)

NS5B is the nonstructural protein 5B of the hepatitis C virus (HCV), functioning as an RNA-dependent RNA polymerase (RdRp). It is essential for viral replication, catalyzing the synthesis of new viral RNA genomes using the positive-sense viral RNA as a template. This enzyme is a prime target for antiviral drug development due to its central role in HCV replication. NS5B has a canonical "right hand" structure, comprising three main subdomains: fingers, palm, and thumb. The active site is encircled within the palm domain. NS5B synthesizes complementary negative-strand RNAs from positive-strand templates and vice versa, enabling genome replication. It initiates de novo synthesis at genome ends or extends primed templates. Magnesium ions are required for catalytic activity.

Other names

Hepatitis C Virus NS5B PolymeraseHCV NS5BNS5B polymerase

Inhibition of RNA-dependent RNA polymerase activity; either through mimicking natural substrates leading to chain termination (nucleotide analogs) or binding to allosteric sites blocking enzymatic function (non-nucleoside inhibitors).