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Biochem Biophys Res Commun. 2009 Jul 24;385(2):230-5. doi: 10.1016/j.bbrc.2009.05.043. Epub 2009 May 19.

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

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1
Department of Forestry, National Chung Hsing University, Taichung, Taiwan, ROC.

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.

PMID:
19450556
DOI:
10.1016/j.bbrc.2009.05.043
[Indexed for MEDLINE]

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