Benzimidazole derivative, BM601, a novel inhibitor of hepatitis B virus and HBsAg secretion

Antiviral Res. 2014 Jul:107:6-15. doi: 10.1016/j.antiviral.2014.04.002. Epub 2014 Apr 15.

Abstract

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family. HBsAg, greatly outnumbered mature virion, has been mysterious since the discovery of HBV. A novel benzimidazole derivative, BM601, is identified inhibiting the secretion of HBV virions and HBsAg, with 50% effective concentration of 0.6μM and 1.5μM, as well as 50% cytotoxicity concentration of 24.5μM. It has no effect on transcription, protein production, nucleocapsid formation or intracellular HBV DNA synthesis. Immunofluorescence analysis suggests that BM601 might inhibit virion and HBsAg secretion by interfering surface protein aggregation in trans Golgi apparatus. Furthermore, BM601 does not trigger cellular stress response or affect HBeAg or host protein secretion. We hypothesize that BM601 is a secretion inhibitor functioning at the level of virion and HBsAg secretion pathway.

Keywords: Anti-hepatitis B virus compound; Benzimidazole derivative; Secretion inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / toxicity
  • Benzimidazoles / isolation & purification
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / toxicity
  • Cell Survival / drug effects
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / physiology*
  • Humans
  • Protein Transport / drug effects
  • Virus Assembly / drug effects*

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Hepatitis B Surface Antigens