Chemical array system, a platform to identify novel hepatitis b virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide

Manabu Kaneko, Yushi Futamura, Senko Tsukuda, Yasumitsu Kondoh, Tomomi Sekine, Hiroyuki Hirano, Kento Fukano, Hirofumi Ohashi, Wakana Saso, Ryo Morishita, Satoko Matsunaga, Fumihiro Kawai, Akihide Ryo, Sam Yong Park, Ryosuke Suzuki, Hideki Aizaki, Naoko Ohtani, Camille Sureau, Takaji Wakita, Hiroyuki OsadaKoichi Watashi*

*この研究の対応する著者

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Current anti-hepatitis B virus (HBV) agents including interferons and nucleos(t)ide analogs efficiently suppress HBV infection. However, as it is difficult to eliminate HBV from chronically infected liver, alternative anti-HBV agents targeting a new molecule are urgently needed. In this study, we applied a chemical array to high throughput screening of small molecules that interacted with sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for HBV. From approximately 30,000 compounds, we identified 74 candidates for NTCP interactants, and five out of these were shown to inhibit HBV infection in cell culture. One of such compound, NPD8716, a coumarin derivative, interacted with NTCP and inhibited HBV infection without causing cytotoxicity. Consistent with its NTCP interaction capacity, this compound was shown to block viral attachment to host hepatocytes. NPD8716 also prevented the infection with hepatitis D virus, but not hepatitis C virus, in agreement with NPD8716 specifically inhibiting NTCP-mediated infection. Analysis of derivative compounds showed that the anti-HBV activity of compounds was apparently correlated with the affinity to NTCP and the capacity to impair NTCP-mediated bile acid uptake. These results are the first to show that the chemical array technology represents a powerful platform to identify novel viral entry inhibitors.

本文言語English
論文番号2769
ジャーナルScientific reports
8
1
DOI
出版ステータスPublished - 2018
外部発表はい

ASJC Scopus subject areas

  • 一般

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