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

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Abstract

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.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume29
Issue number2
DOIs
Publication statusPublished - 2014 Apr

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Keywords

  • Cholesterol sulfate
  • Hepatitis C virus
  • Marine organism
  • NS3 helicase

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Furuta, A., Salam, K. A., Akimitsu, N., Tanaka, J., Tani, H., Yamashita, A., Moriishi, K., Nakakoshi, M., Tsubuki, M., Sekiguchi, Y., Tsuneda, S., & Noda, N. (2014). Cholesterol sulfate as a potential inhibitor of hepatitis C virus NS3 helicase. Journal of Enzyme Inhibition and Medicinal Chemistry, 29(2), 223-229. https://doi.org/10.3109/14756366.2013.766607