Molecular Targets in Inhibition of Hepatitis C Virus Replication

Abstract

Hepatitis C virus (HCV) is the major cause of transfusion-associated hepatitis and accounts for a significant proportion of hepatitis cases worldwide. Most, if not all, infections become persistent and about 60% of cases develop chronic liver disease with various outcomes ranging from an asymptomatic carrier state to chronic active hepatitis and liver cirrhosis, which is strongly associated with the development of hepatocellular carcinoma. Since the initial cloning of the viral genome in 1989, our knowledge of the molecular biology of HCV has increased rapidly and led to the identification of several potential targets for antiviral intervention. In contrast, the low replication of the virus in cell culture, the lack of convenient animal models and the high genome variability present major challenges for drug development. This review will describe candidate drug targets and summarize ‘classical’ and ‘novel’ approaches currently being pursued to develop efficient HCV-specific therapies.