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Research Article

Molecular mechanism of resveratrol inhibition of Zika virus NS3 helicase: behind the scenes

    Nikita Devnarain

    Molecular Bio-computation & Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa

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    &
    Mahmoud ES Soliman

    *Author for correspondence: Tel.: +0312607413;

    E-mail Address: soliman@ukzn.ac.za

    Molecular Bio-computation & Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa

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    Published Online:18 Jan 2019https://doi.org/10.2217/fvl-2018-0170

    Abstract

    Aim: Zika virus (ZIKV) still poses a health risk to women and their babies without US FDA-approved vaccines or treatments. Experimentation has proved resveratrol inhibition of ZIKV NS3 helicase without specifying the molecular events during inhibition. Materials & methods: Herein, we leaped forward to study the molecular dynamics of the bound and unbound enzyme, identifying precise binding residues and interactions, and the enzyme's adaptation to support binding, since loop dynamics affect viral RNA replication. Results: Resveratrol stabilizes the P-loop and causes the RNA-binding loop to block the RNA-binding pocket for 200 ns, which is concurrent with experimental evidence that resveratrol binding significantly reduces ATP hydrolysis activity. Conclusion: This study illuminates the structural dynamics of ZIKV helicase and druglikeness of resveratrol, which will advance anti-ZIKV drug development.

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