Fisetin and rutin as 3C protease inhibitors of enterovirus A71

Ying Ju Lin, Yi Chih Chang, Nai-Wan Hsiao, Jing Ling Hsieh, Ching Ying Wang, Szu Hao Kung, Fuu Jen Tsai, Yu Ching Lan, Cheng Wen Lin

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 IC 50 values of plaque reduction against EV-A71 were 85μM for fisetin and 110μM 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.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalJournal of Virological Methods
Volume182
Issue number1-2
DOIs
Publication statusPublished - 2012 Jun 1

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Rutin
Enterovirus
Protease Inhibitors
Viral Cytopathogenic Effect
Fluorescence Resonance Energy Transfer
fisetin
3C proteases
Pulmonary Edema
Encephalitis
Virus Replication
Flavonoids
Inhibitory Concentration 50
Antiviral Agents
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Lin, Y. J., Chang, Y. C., Hsiao, N-W., Hsieh, J. L., Wang, C. Y., Kung, S. H., ... Lin, C. W. (2012). Fisetin and rutin as 3C protease inhibitors of enterovirus A71. Journal of Virological Methods, 182(1-2), 93-98. https://doi.org/10.1016/j.jviromet.2012.03.020
Lin, Ying Ju ; Chang, Yi Chih ; Hsiao, Nai-Wan ; Hsieh, Jing Ling ; Wang, Ching Ying ; Kung, Szu Hao ; Tsai, Fuu Jen ; Lan, Yu Ching ; Lin, Cheng Wen. / Fisetin and rutin as 3C protease inhibitors of enterovirus A71. In: Journal of Virological Methods. 2012 ; Vol. 182, No. 1-2. pp. 93-98.
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abstract = "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 IC 50 values of plaque reduction against EV-A71 were 85μM for fisetin and 110μM 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.",
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Lin, YJ, Chang, YC, Hsiao, N-W, Hsieh, JL, Wang, CY, Kung, SH, Tsai, FJ, Lan, YC & Lin, CW 2012, 'Fisetin and rutin as 3C protease inhibitors of enterovirus A71', Journal of Virological Methods, vol. 182, no. 1-2, pp. 93-98. https://doi.org/10.1016/j.jviromet.2012.03.020

Fisetin and rutin as 3C protease inhibitors of enterovirus A71. / Lin, Ying Ju; Chang, Yi Chih; Hsiao, Nai-Wan; Hsieh, Jing Ling; Wang, Ching Ying; Kung, Szu Hao; Tsai, Fuu Jen; Lan, Yu Ching; Lin, Cheng Wen.

In: Journal of Virological Methods, Vol. 182, No. 1-2, 01.06.2012, p. 93-98.

Research output: Contribution to journalArticle

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AU - Kung, Szu Hao

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AU - Lin, Cheng Wen

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