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

• BM601 is the first benzimidazole derivative reported as HBV secretion inhibitor.
• BM601 interferes surface protein aggregation in trans Golgi apparatus.
• BM601 may help researchers to unveil novel aspects of HBV budding and secretion.
• This work may throw lights on further anti-HBV studies of benzimidazole derivatives.

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 0.6 μM and 1.5 μM, as well as 50% cytotoxicity concentration of 24.5 μM. 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.