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Abstract Title:

Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.

Abstract Source:

Biochem Biophys Res Commun. 2009 Jul 24 ;385(2):230-5. Epub 2009 May 19. PMID: 19450556

Abstract Author(s):

Sheng-Yang Wang, Ching-Ping Tseng, Keng-Chang Tsai, Chia-Fan Lin, Ching-Ya Wen, Hsin-Sheng Tsay, Naoya Sakamoto, Chin-Hsiao Tseng, Ju-Chien Cheng

Article Affiliation:

Sheng-Yang Wang

Abstract:

Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC(50)=0.89 microM. Notably, pheophytin a and IFNalpha-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Antiviral Agents : CK(1957) : AC(1615)

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