Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide

Kei Miyakawa, Satoko Matsunaga, Yutaro Yamaoka, Mina Dairaku, Kento Fukano, Hirokazu Kimura, Tomoyuki Chimuro, Hironori Nishitsuji, Koichi Watashi, Kunitada Shimotohno, Takaji Wakita, Akihide Ryo

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5 Citations (Scopus)

Abstract

Sodium taurocholate cotransporting polypeptide (NTCP) is a major entry receptor of hepatitis B virus (HBV) and one of the most attractive targets for anti-HBV drugs. We developed a cell-mediated drug screening method to monitor NTCP expression on the cell surface by generating a HepG2 cell line with tetracycline-inducible expression of NTCP and a monoclonal antibody that specifically detects cell-surface NTCP. Using this system, we screened a small molecule library for compounds that protected against HBV infection by targeting NTCP. We found that glabridin, a licorice-derived isoflavane, could suppress viral infection by inducing caveolar endocytosis of cell-surface NTCP with an IC50 of ~40 μM. We also found that glabridin could attenuate the inhibitory effect of taurocholate on type I interferon signaling by depleting the level of cell-surface NTCP. These results demonstrate that our screening system could be a powerful tool for discovering drugs targeting HBV entry.

Original languageEnglish
Pages (from-to)23681-23694
Number of pages14
JournalOncotarget
Volume9
Issue number34
DOIs
Publication statusPublished - 01-05-2018

All Science Journal Classification (ASJC) codes

  • Oncology

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    Miyakawa, K., Matsunaga, S., Yamaoka, Y., Dairaku, M., Fukano, K., Kimura, H., Chimuro, T., Nishitsuji, H., Watashi, K., Shimotohno, K., Wakita, T., & Ryo, A. (2018). Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide. Oncotarget, 9(34), 23681-23694. https://doi.org/10.18632/oncotarget.25348