| Literature DB >> 19450556 |
Sheng-Yang Wang1, Ching-Ping Tseng, Keng-Chang Tsai, Chia-Fan Lin, Ching-Ya Wen, Hsin-Sheng Tsay, Naoya Sakamoto, Chin-Hsiao Tseng, Ju-Chien Cheng.
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.Entities:
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Year: 2009 PMID： 19450556 DOI： 10.1016/j.bbrc.2009.05.043
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575