Interaction and assembly of HBV structural proteins: Novel target sites of anti-HBV agents

Human hepatitis B virus (HBV) causes chronic hepatitis disease which is a major public health problem worldwide. HBV has 4 genes encoding viral DNA polymerase, protein X and two structural proteins, the surface and core proteins. HBV DNA polymerase has been a primary target for the development of anti-HBV agents due to its enzymatic nature, and several nucleoside derivatives that inhibit HBV polymerase are currently used as anti-HBV therapeutics. On the other hand, accumulating information on the capsid assembly and the maturation process of HBV particles provides additional approaches for the development of anti-HBV agents. Proper interaction between core proteins is required for assembly of the nucleocapsid, and the specificity of the interactions between the capsid and surface proteins is essential for the maturation of active HBV in infected cells. In this article, the assembly process of active HBV particles and approaches to utilize the interactions of HBV structural proteins as target site for the development of anti-HBV agents are reviewed. In particular, novel approaches to target the assembly process an the interaction between HBV structural proteins are introduced.