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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.
Tseng, C.P.
Tsai, K.C.
Lin, C.F.
Wen, C.Y.
Tsaye, H.S.
Sakamoto, N.
Tseng, C.H.
Cheng, J.C.
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.
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.
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2009.05.043
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