Recent progress in potential anti-hepatitis B virus agents: Structural and pharmacological perspectives

Abstract

Hepatitis B virus (HBV) infections affect about 240 million patients worldwide and increase the risk of liver cirrhosis and hepatocellular carcinoma. It is estimated that about 686 thousand people died annually of liver damage resulted from HBV infections. At present, two classes of antiviral drugs have been approved by the Food and Drug Administration (FDA) for the treatment of hepatitis B, immunomodulators (interferon [IFN]-a and pegylated-interferon [PEG-IFN]-a) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and entecavir [ETV]). However, it still remains a daunting challenge for curing HBV, because of the low sustained response rates (20-30%) and many side effects of IFN and peg-IFN. Although nucleoside analogues are well tolerated and exhibit an early and potent antiviral effect, the selection of resistant mutants and nephrotoxicity during long-term therapy limit their use. Here, we focus on summarizing the currently approved anti-HBV drugs and characterization of novel HBV inhibitors and analysing their structures, targets, anti-HBV effects and mechanisms of action, which may shed new light on the discovery of small compounds as potential anti-HBV drugs for treatment of HBV.

Keywords: Hepatitis B virus; Inhibitors; Mechanisms of action; Nucleos(t)ide analogs.