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|標題:||Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq||作者:||Wang, S.Y.
|關鍵字:||Hepatitis C virus;Lonicera hypoglauca Miq.;Pheophytin a;Replicon;cells;serine-protease;rna replication;cell-culture;inhibition;infection;ribavirin;variants;japonica;chinese;system||Project:||Biochemical and Biophysical Research Communications||期刊/報告no：:||Biochemical and Biophysical Research Communications, Volume 385, Issue 2, Page(s) 230-235.||摘要:||
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 ethano-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV vital 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 mu M. Notably, pheophytin a and IFN alpha-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. (C) 2009 Elsevier Inc. All rights reserved.
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