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Identification of novel inhibitory candidates against two major Flavivirus pathogens via CADD protocols: in silico analysis of phytochemical binding, reactivity, and pharmacokinetics against NS5 from ZIKV and DENV

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Abstract

Zika and dengue virus are flaviviruses which with the passage of time have become a serious challenge affecting millions of people around the world. To lessen the impact of these viral infections globally and to combat these virus-associated epidemics in the future, new medical findings and pharmacological approaches are needed. The phytochemicals extracted from a variety of various plants consist of amazing medicinal properties and can be used in the production of novel anti-viral drugs. The two domains of NS5 protein (NS5 MTase and NS5 RdRp) can be targeted in the clinical trials to produce effective novel inhibitors against Zika and dengue fever. Herein, we aim at using a wide variety of phytochemicals (n = 2035) as inhibitors against NS5 protein from DENV and ZIKV. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the selected compounds were studied to evaluate the pharmacological characteristics. Molecular docking was carried out to determine the binding properties of these ligands with NS5 protein and reactivity was analyzed using molecular orbital energy descriptors. A total of 108 compounds were found suitable in ADMET and from 108 compounds, 35 compounds with the highest in the case of NS5 MTase from ZIKV and DENV were selected. While for NS5 RdRp, 29 compounds were selected. Those compounds, which exhibited remarkable binding affinities values against the proteins of both the ZIKV and 4 serotypes of DENV simultaneously, were predominantly selected in this study. It is concluded that these compounds can be used in clinical trials for the production of a mutual anti-viral drug against both DENV and ZIKV.

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Authors and Affiliations

  1. Center for Professional Studies, Lahore, Pakistan

    Nouman Rasool & Waqar Hussain

  2. Medicare Health Services, Lahore, Pakistan

    Arshia Majeed

  3. Department of Life Sciences, University of Management and Technology, Lahore, 54770, Pakistan

    Fareeha Riaz

  4. National Center of Artificial Intelligence, Punjab University College of Information Technology, University of the Punjab, Lahore, Pakistan

    Waqar Hussain

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  1. Nouman Rasool
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  2. Arshia Majeed
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  3. Fareeha Riaz
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  4. Waqar Hussain
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Nouman Rasool—idea formation; formal analysis; review of draft; supervision.

Arshia Majeed—revision; review of draft; and validation.

Fareeha Riaz—data curation and initial draft write-up.

Waqar Hussain—methods; experimentation; and results analysis.

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Correspondence to Nouman Rasool.

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Rasool, N., Majeed, A., Riaz, F. et al. Identification of novel inhibitory candidates against two major Flavivirus pathogens via CADD protocols: in silico analysis of phytochemical binding, reactivity, and pharmacokinetics against NS5 from ZIKV and DENV. Struct Chem 31, 2189–2204 (2020). https://doi.org/10.1007/s11224-020-01577-x

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