Drug discovery and development of antiviral agents for the treatment of chronic hepatitis B virus infection.

A safe and effective vaccine for hepatitis B virus (HBV) has been available for nearly twenty years and currently campaigns to provide universal vaccination in developing countries are underway. Nevertheless, chronic HBV infection remains a leading cause of chronic hepatitis worldwide and there is a strong need for safe and effective antiviral therapies. Attempts to identify and develop antiviral agents to treat chronic HBV infection remains focused on nucleoside analogs such as 3TC (lamivudine), adefovir dipivoxil, (bis-POMPMEA), and others. However, advances in our understanding of the molecular biology of HBV and the development of new assays for HBV polymerase activity, such as the reconstitution of active HBV polymerase in vitro, should facilitate large screening efforts for non-nucleoside reverse transcriptase inhibitors. Recent advances have furthered our understanding of clinical resistance to lamivudine, have provided new approaches to treatment, and have offered new perspectives on the major challenges to the identification and development of antiviral agents for chronic HBV infection. Here, in an update to our previous review article that appeared in this series [59a], we focus on recent advances that have occurred in the areas of virus structure and replication, in vitro viral polymerase assays, cell culture systems, and animal models.