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


CONCLUSIONS
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.
Boehringer Ingelheim Canada Limited, Laval, Quebec, Canada.
Pierre L
PL
Beaulieu
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D024882:Drug Resistance, Viral; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D010330:Patents as Topic; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*
D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase