Abstract
Enterovirus 71 (EV71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. The anti-EV71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. By using the predicting program Autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3Cpro activity. Replication of viral RNA and production of viral capsid protein and the infectious virion were strongly inhibited by chrysin, without noticeable cytotoxicity. Cytopathic effects on cells were also prevented. Diisopropyl chrysin-7-yl phosphate (CPI), the phosphate ester for chrysin, was generated through a simplified Atheron-Todd reaction to achieve stronger anti-viral activity. CPI was also able to bind with and inhibit viral 3Cpro activity in vitro. As expected, CPI demonstrated more potent antiviral activity against EV71.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3C Viral Proteases
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Cell Line, Tumor
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Cell Survival / drug effects
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Chrysenes / chemistry
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Chrysenes / pharmacology*
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Cysteine Endopeptidases / chemistry
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Cysteine Proteinase Inhibitors / chemistry
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Cysteine Proteinase Inhibitors / pharmacology*
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Drug Evaluation, Preclinical
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Enterovirus A, Human / drug effects
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Enterovirus A, Human / physiology*
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Flavonoids / chemistry
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Flavonoids / pharmacology*
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Humans
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Molecular Docking Simulation
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Organophosphates / chemistry
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Organophosphates / pharmacology*
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Viral Proteins / antagonists & inhibitors
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Viral Proteins / chemistry
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Virus Replication / drug effects
Substances
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Antiviral Agents
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Chrysenes
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Cysteine Proteinase Inhibitors
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Flavonoids
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Organophosphates
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Viral Proteins
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diisopropyl chrysin-7-yl phosphate
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chrysin
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Cysteine Endopeptidases
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3C Viral Proteases
Grants and funding
The work was supported by the National Science and Technology Major Project of China, project No.2013ZX10004-601, No.2011ZX10004-001 and No.2013ZX10004-101. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.