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Antiviral Res. 2015 Aug;120:140-6. doi: 10.1016/j.antiviral.2015.06.007. Epub 2015 Jun 15.

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.

Author information

1
Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: xjwang@bmi.ac.cn.
2
Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
3
Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: sqwang@bmi.ac.cn.

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.

KEYWORDS:

HepG2; Hepatitis B virus; Irbesartan; NTCP; Viral entry inhibitor

PMID:
26086883
DOI:
10.1016/j.antiviral.2015.06.007
[Indexed for MEDLINE]

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