Cholesterol sulfate as a potential inhibitor of hepatitis C virus NS3 helicase

Atsushi Furuta, Kazi Abdus Salam, Nobuyoshi Akimitsu, Junichi Tanaka, Hidenori Tani, Atsuya Yamashita, Kohji Moriishi, Masamichi Nakakoshi, Masayoshi Tsubuki, Yuji Sekiguchi, Satoshi Tsuneda*, Naohiro Noda

*この研究の対応する著者

研究成果: Article査読

7 被引用数 (Scopus)

抄録

Hepatitis C virus nonstructural protein 3 (NS3) helicase is a promising target for developing new therapeutics. In this study, we identified cholesterol sulfate (CS) as a novel NS3 helicase inhibitor (IC50 = 1.7 ± 0.2 μM with a Hill coefficient of 3.9) by screening the extracts from marine organisms. The lack of the sulfate group, sterol structure or alkyl side chain of CS diminished the inhibition, suggesting that an anion binding and hydrophobic region in NS3 may be a target site of CS. It was further found that CS partly inhibits NS3-RNA binding activity, but exerted no or less inhibition against ATPase and serine protease activities. Moreover, we demonstrated that CS probably does not bind to RNA. Our findings suggest that CS may inhibit NS3 helicase not by abolishing the other NS3 activities but by inducing conformational changes via interaction with possible allosteric sites of NS3.

本文言語English
ページ(範囲)223-229
ページ数7
ジャーナルJournal of Enzyme Inhibition and Medicinal Chemistry
29
2
DOI
出版ステータスPublished - 2014 4

ASJC Scopus subject areas

  • 薬理学
  • 創薬

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