Novel protease and polymerase inhibitors for the treatment of hepatitis C virus infection

Abstract

Chronic hepatitis C virus (HCV) infection remains a global health concern with nearly 200 million carriers worldwide. Present treatment consists of the use of pegylated interferon plus the purine analogue ribavirin. Serious side effects and the fact that an overall 40 – 50% of patients do not accomplish sustained virological response with the present treatment warrant the need for novel anti-HCV therapies. The HCV serine protease and the RNA-dependent RNA polymerase have shown to be excellent targets for selective antiviral therapy. Early clinical studies have resulted in encouraging results. However, and not unexpectedly, preclinical evidence suggests that the virus may become rapidly resistant to such inhibitors. Therefore, combination therapy of drugs with different mode of action and resistance profiles may be required. This review focuses on the present status of these two families of HCV inhibitors that are in development.

Keywords::

• antiviral treatment
• hepatitis C
• polymerase inhibitors
• protease inhibitors

Acknowledgements

This work was supported in part by grants from VIRGIL European Network of Excellence on Antiviral Drug Resistance (LSHM-CT-2004-503359), the European AIDS treatment network (NEAT), Spanish RIS (ISCIII-RETIC RD06) and Fundación Investigación y Educación en SIDA (IES).