Small Molecule Inhibitors of Hepatitis B Virus Nucleocapsid Assembly: A New Approach to Treat Chronic HBV Infection

Hepatitis B virus (HBV) infection is still a major health problem worldwide. The current available antiviral drugs for the treatment of chronic HBV infection do not achieve satisfactory results. Thus, it is desirable to develop novel anti-HBV drugs based on the recent advances of basic research on molecular biology of HBV. HBV nucleocapsid assembly is now considered as a potential target of anti-HBV therapy. Structural and functional analysis provided essential insight of molecular interaction of the components of HBV nucleocapsid. Prototypes of small molecule modulators of HBV nucleocapsid assembly were developed and partly tested in clinical phase I. In the present review, the recent advances in HBV molecular biology and approach to develop inhibitors for anti-HBV treatment based on the disruption of viral nucleocapsids by either prevention of assembly or induction of misassembly will be summarized. We will discuss the future concepts of anti-HBV treatment based on such new approaches.