Fisetin and rutin as 3C protease inhibitors of enterovirus A71

被引：65
作者：
Lin, Ying-Ju [2 ,3 ]
Chang, Yi-Chih [1 ]
Hsiao, Nai-Wan [4 ]
Hsieh, Jing-Ling [4 ]
Wang, Ching-Ying [5 ]
Kung, Szu-Hao [6 ,7 ]
Tsai, Fuu-Jen [2 ,3 ]
Lan, Yu-Ching [8 ]
Lin, Cheng-Wen [1 ,9 ]
机构：
[1] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung 404, Taiwan
[2] China Med Univ, Sch Chinese Med, Taichung 404, Taiwan
[3] China Med Univ Hosp, Dept Med Res, Taichung, Taiwan
[4] Natl Changhua Univ Educ, Inst Biotechnol, Changhua, Taiwan
[5] China Med Univ, Sch Chinese Pharmaceut Sci & Chinese Med Resource, Taichung 404, Taiwan
[6] Natl Yang Ming Univ, Dept Biotechnol, Taipei 112, Taiwan
[7] Natl Yang Ming Univ, Lab Sci Med, Taipei 112, Taiwan
[8] China Med Univ, Dept Hlth Risk Management, Taichung 404, Taiwan
[9] Asia Univ, Coll Hlth Sci, Dept Biotechnol, Taichung, Taiwan
来源：
JOURNAL OF VIROLOGICAL METHODS | 2012年 / 182卷 / 1-2期
关键词：
Enterovirus A71; 3C protease; Flavonoids; Fisetin; Rutin; ANTIVIRAL ACTIVITY; SUBSTITUTED FLAVANOIDS; VIRUS; FLAVONOIDS; INFECTION; RUPINTRIVIR; MECHANISM; DESIGN; POTENT; HAND;
D O I：
10.1016/j.jviromet.2012.03.020
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Enterovirus A71 (EV-A71) causes severe complications: encephalitis, pulmonary edema, and death. No effective drug has been approved for clinical use. This study investigated the antiviral effects of flavonoids against EV-A71. An in vitro inhibitor screening assay using recombinant EV-A71 3C protease (3Cpro) demonstrated fisetin and rutin inhibiting 3Cpro enzymatic activity in a dose-dependent manner. Cell-based fluorescence resonance energy transfer (FRET) assay with an EV-A71 3Cpro cleavage motif probe also confirmed that fisetin and rutin inhibited the replication of EV-A71 in cells. A virus replication assay indicated that fisetin and rutin reduced significantly the EV-A71-induced cytopathic effect and viral plaque titers in RD cells culture. The IC50 values of plaque reduction against EV-A71 were 85 p,M for fisetin and 110 mu M for rutin. Therapeutic indices (CC50/IC50 of plaque reduction assays) of fisetin and rutin exceeded 10. The study suggests that fisetin and rutin inhibit the replication of EV-A71. (C) 2012 Elsevier B.V. All rights reserved.
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收藏
页码：93 / 98
页数：6
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