title: Benzimidazole derivative, BM601, a novel inhibitor of hepatitis B virus and HBsAg secretion.
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.
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Xu
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Gui-Feng
authors.initials: GF
authors.lastname: Wang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Xian-Kun
authors.initials: XK
authors.lastname: Tong
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Jing-Feng
authors.initials: JF
authors.lastname: Jing
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Chun-Lan
authors.initials: CL
authors.lastname: Feng
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Pei-Lan
authors.initials: PL
authors.lastname: He
authors.affiliation: Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, China. Electronic address: wlu@chem.ecnu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China. Electronic address: tangwei@mail.shcnc.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China; Shanghai University of Traditional Chinese Medicine, China. Electronic address: jpzuo@mail.shcnc.ac.cn.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D021381:Protein Transport / Q000187:drug effects; D019065:Virus Assembly / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D006514:Hepatitis B Surface Antigens
keywords: Anti-hepatitis B virus compound; Benzimidazole derivative; Secretion inhibitor