RNA dependent RNA polymerase of HCV: A potential target for the development of antiviral drugs

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma, cirrhosis and end stage liver disease. More than 200 million people are living with HCV worldwide with high morbidity and mortality. There is no vaccine available for this virus; the approved treatment option for the majority of HCV genotypes is the combination of pegylated (Peg) interferon and ribavirin. The therapy has a different response rate on different HCV genotypes and has a number of side effects. Recently, as well as Peg interferon and ribavirin, two protease inhibitors have been introduced to treat patients with HCV genotype 1 infection. The protease inhibitors have rapid onset of resistance and are not approved for use for infections with other HCV genotypes. The HCV NS5B gene encodes RNA dependent RNA polymerase (RdRp), which is the key player in viral replication and is a promising target for the development of antiviral drugs. HCV NS5B has been studied in various biochemical assays, cell based assays and animal model systems. So far, a number of nucleoside and non-nucleoside inhibitors have been screened for effects on viral replication. This review presents a deep insight into the structure and function of HCV polymerase and the effect of various nucleoside and non-nucleoside inhibitors on viral replication.