Abstract
Currently, there are two safe and effective therapeutic strategies for chronic hepatitis B treatment, namely, nucleoside analogs and interferon alpha (pegylated or non-pegylated). These treatments can control viral replication and improve survival; however, they do not eliminate the virus and therefore require long-term continued therapy. In addition, there are significant concerns about virus rebound on discontinuation of therapy and the development of fibrosis and hepatocellular carcinoma despite therapy. Therefore, the search for new, more effective, and safer antiviral agents that can cure hepatitis B virus (HBV) continues. Anti-HBV drug discovery and development is fundamentally impacted by our current understanding of HBV replication, disease physiopathology, and persistence of HBV covalently closed circular DNA (cccDNA). Several HBV replication targets are the basis for novel anti-HBV drug development strategies. Many of them are already in clinical trial phase 1 or 2, while others with promising results are still in preclinical stages. As research intensifies, potential HBV curative therapies and modalities in the pipeline are now on the horizon.