Hepatitis C Virus Nonstructural Protein 5B Polymerase (NS5B)

Hepatitis C virus nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) that plays a central role in the replication of the hepatitis C virus (HCV) genome. It catalyzes the synthesis of new viral RNA strands using the positive-sense viral RNA as a template, making it essential for both translation and production of progeny genomes. NS5B is approximately 66 kDa in size and consists of about 590 amino acids, located at the C-terminus of HCV’s polyprotein. The three-dimensional structure resembles a right hand with three main domains: Palm domain, Finger domain, and Thumb domain. Because NS5B is essential for HCV genome replication—and because no human homolog exists—it represents an ideal target both scientifically and therapeutically. Its inhibition leads directly to cessation of viral propagation within infected hepatocytes.

Inhibition of viral RNA replication by mimicking natural substrates or binding allosterically at sites such as thumb I/II or palm regions, stabilizing inactive conformations or blocking nucleotide incorporation.