title: Irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, is a potent inhibitor for hepatitis B virus entry by disturbing Na(+)-dependent taurocholate cotransporting polypeptide activity.
abstract: The liver-specific Na(+)-dependent taurocholate cotransporting polypeptide (NTCP) was recently identified as an entry receptor for hepatitis B virus (HBV) hepatotropic infection. In this study, an NTCP-overexpressing HepG2 cell line named HepG2.N9 susceptible to HBV infection was established using transcription activator-like effector nucleases (TALEN) technology. Using this cell line, irbesartan, the new NTCP-interfering molecule reported recently, was demonstrated here to effectively inhibit HBV infection with an IC50 of 3.3μM for hepatitis B e antigen (HBeAg) expression and exhibited no obvious cytotoxicity up to 1000μM. Irbesartan suppressed HBV uptake weakly but inhibited HBV covalently closed circular DNA (cccDNA) formation efficiently at physiological temperature. These results suggested that irbesartan targeted HBV infection at a post-uptake prior to cccDNA formation step such as the cell membrane fusion. Based on these findings, irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, could be a potential candidate for treatment of HBV infection although further in vivo experiments are required.
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: xjwang@bmi.ac.cn.
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Ting-yu
authors.initials: TY
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Mao
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Nan-nan
authors.initials: NN
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: sqwang@bmi.ac.cn.
authors.forename: Sheng-qi
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D058492:Drug Repositioning; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D020128:Inhibitory Concentration 50; D000077405:Irbesartan; D008826:Microbial Sensitivity Tests; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors*; D027981:Symporters / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000494:pharmacology* / Q000633:toxicity; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001713:Biphenyl Compounds; D029363:Organic Anion Transporters, Sodium-Dependent; D011991:Receptors, Virus; D027981:Symporters; D013777:Tetrazoles; C071908:sodium-bile acid cotransporter; D000077405:Irbesartan
keywords: HepG2; Hepatitis B virus; Irbesartan; NTCP; Viral entry inhibitor