2014年4月
Cholesterol sulfate as a potential inhibitor of hepatitis C virus NS3 helicase
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
- 巻
- 29
- 号
- 2
- 開始ページ
- 223
- 終了ページ
- 229
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.3109/14756366.2013.766607
- 出版者・発行元
- INFORMA HEALTHCARE
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 mu M 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.
- リンク情報
- ID情報
-
- DOI : 10.3109/14756366.2013.766607
- ISSN : 1475-6366
- eISSN : 1475-6374
- PubMed ID : 23432541
- Web of Science ID : WOS:000332865600010