Inhibitors of the HCV NS5B polymerase: new hope for the treatment of hepatitis C infections

The spread of hepatitis C virus (HCV) infections and serious health consequences associated with chronic states of the disease have become a global concern. Small-molecule drugs that are specific for anti-HCV chemotherapy are not available and the current treatments for this disease suffer from limited success. The NS5B RNA-dependent RNA polymerase of HCV is an essential enzyme for viral replication. It has emerged in the last years as the most 'drugable' target of the entire HCV genome. While no agents from this class have yet demonstrated sustained efficacy in infected patients, early stage proof-of-concept has been achieved in the clinic, providing validation of the approach for antiviral therapy. This review provides a comprehensive account of the progress made towards the discovery of anti-HCV therapeutics based on inhibition of the virally encoded NS5B polymerase.