The Development of Novel HCV NS3-4A Protease Inhibitors

Continual genetic variation supports hepatitis C virus (HCV) persistent infection, a leading cause of cirrhosis and hepatocellular carcinoma. The current standard of care has limited efficacy and is associated with severe adverse effects. Efforts to improve patients' outcomes have focused on the design and development of small molecule compounds targeted towards essential viral proteins. Following the clinical success of HIV protease inhibitors, the HCV NS3-4A protease domain emerged as one of the most successful antiviral drug targets. This mini-review describes several HCV protease inhibitors in the various stages of clinical trials, and discusses their antiviral activities, pharmacokinetic properties, side effects and resistance profiles.