Journal
JOURNAL OF VIROLOGICAL METHODS
Volume 182, Issue 1-2, Pages 93-98Publisher
ELSEVIER
DOI: 10.1016/j.jviromet.2012.03.020
Keywords
Enterovirus A71; 3C protease; Flavonoids; Fisetin; Rutin
Funding
- China Medical University [CMU99-NSC-08, CMU100-S-33, CMU98-CT-22]
- Republic of China National Science Council [NSC 99-2628-B-039006-MY3]
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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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