Hepatitis B: New Approaches for Antiviral Chemotherapy

Progress in the development of effective therapeutic regimes for chronic hepatitis B has been slow, mainly due to the lack of promising lead compounds and useful assays for high throughput in-vitro screening. Nucleoside analogue chemotherapy has targeted the inhibition of the hepatitis B virus (HBV) polymerase and achieved inhibition of this unique viral enzyme. The persistence and resistance of HBV covalently closed circular (or supercoiled) DNA, the key replicative intermediate and sole transcriptional template, to existing treatments also poses challenges for the effective development of antiviral chemotherapy. In spite of these difficulties, the process of viral DNA replication, as well as supercoiled DNA generation and processing, is now being elucidated at the molecular level, presenting unique opportunities for new drug targeting and design. This review attempts to highlight these new approaches to the development of treatment regimes for this important disease.