Recent advances in the development of NS5B polymerase inhibitors for the treatment of hepatitis C virus infection

Abstract

Background: 170 to 200 million people worldwide are believed to suffer from chronic hepatitis C virus (HCV) infection, a blood-born disease that targets the liver and progresses to organ cirrhosis and primary cancer in a significant proportion of patients. The currently available treatment has limited efficacy and suffers from restricting side effects. HCV infection is the principal cause of liver transplant in industrialized nations and between 8000 and 10,000 deaths result annually from the disease in the United States alone. Virus-specific, more efficacious, and better-tolerated anti-HCV therapies are thus required to address the unmet medical need. Objective: To review progress achieved since 2005 in the development of HCV NS5B polymerase inhibitors as potential therapy for the treatment of HCV infection with a primary focus on available patent and medical literature. Results/conclusion: Several classes of small-molecule inhibitors of HCV NS5B have progressed into clinical development and demonstrated efficacy in reducing viral load in infected patients. The results so far provide an encouraging foundation for the development of novel, more tolerable therapies and addressing emergence of resistance through combination of antiviral agents with complementary mechanisms of action.

Keywords::

• allosteric
• antiviral agents
• combination therapy
• drug resistance
• HCV
• hepatitis C virus
• inhibitors
• non-nucleoside
• NS5B polymerase
• nucleoside
• viral infection

Acknowledgements

The author thanks Dr George Kukolj for critical review of the manuscript, Dr Araz Jakalian and René Coulombe for providing Figure 1, and Hélène Gagnon and Christine Martens for literature searches.