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

Hepatitis C virus RNA-directed RNA polymerase (NS5B) is the essential enzyme responsible for the replication of the HCV RNA genome [2, 4, 12]. As an RNA-dependent RNA polymerase (RdRp), it catalyzes the synthesis of a negative-strand RNA intermediate from the positive-strand viral genome, which then serves as a template for the production of new positive-strand progeny [10, 17, 18]. NS5B is a key component of the membrane-associated viral replication complex, working in coordination with other non-structural proteins such as NS3, NS4A, NS4B, and NS5A [6, 16, 17]. Because humans lack a direct homolog of this enzyme, NS5B is a primary target for direct-acting antiviral (DAA) therapies [4, 9, 12]. Drugs targeting NS5B are divided into two main classes: nucleoside/nucleotide inhibitors (NIs) and non-nucleoside inhibitors (NNIs) [2, 8, 11]. NIs, such as sofosbuvir, act as chain terminators by mimicking natural substrates, while NNIs, such as dasabuvir, bind to allosteric sites to inhibit enzymatic function [8, 11, 13]. These therapies have revolutionized the treatment of chronic hepatitis C, offering high cure rates and improved safety profiles compared to older interferon-based regimens [8, 11, 15]. However, the high mutation rate of the virus can lead to the emergence of resistance-associated substitutions, necessitating combination therapy [9, 13, 15].

Other names

RNA-dependent RNA polymeraseRdRpHCV polymeraseNon-structural protein 5BHCV RNA synthesis

Inhibition of viral RNA synthesis through nucleoside/nucleotide analogue chain termination or non-nucleoside allosteric inhibition of the NS5B polymerase.