The life cycle of hepatitis B virus and antiviral targets

Hepatitis B virus (HBV) remains a major public health issue with more than 350 million people chronically infected worldwide. Therapies using IFN-alpha or nucleos(t)ide analogs, which are currently approved for the treatment of chronic HBV infection, have failed to completely eliminate the virus. By describing the HBV life cycle, this article focuses on potential HBV targets and recent advances in the development of alternative antiviral strategies to fight chronic HBV infection. The targets that are currently under investigation to develop inhibitors are viral entry, circular covalently closed DNA formation and its regulation, nucleocapsid assembly and viral morphogenesis, as well as the innate response of infected cells against HBV infection. Other steps in the viral life cycle are potential targets; however, the development of novel antivirals remains challenging. The development of new HBV inhibitors represents a major advance in the field of antiviral therapy, to prevent antiviral drug resistance and to achieve long-term control of viral replication.