Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study

Malvi Surti; Mitesh Patel; Mohd Adnan; Afrasim Moin; Syed Amir Ashraf; Arif Jamal Siddiqui; Mejdi Snoussi; Sumukh Deshpande; Mandadi Narsimha Reddy

doi:10.1039/D0RA06379G

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study

Malvi Surti,†^a Mitesh Patel,

†^a Mohd Adnan,

^b Afrasim Moin,^c Syed Amir Ashraf,

^d Arif Jamal Siddiqui,

^b Mejdi Snoussi,^bf Sumukh Deshpande*^e and Mandadi Narsimha Reddy

*^a

Author affiliations

* Corresponding authors

^a Bapalal Vaidya Botanical Research Centre, Department of Biosciences, Veer Narmad South Gujarat University, Surat, Gujarat, India
E-mail: nrutya_reddy@yahoo.com

^b Department of Biology, College of Science, University of Hail, P. O. Box 2440, Hail, Saudi Arabia

^c Department of Pharmaceutics, College of Pharmacy, University of Hail, P. O. Box 2440, Hail, Saudi Arabia

^d Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, P. O. Box 2440, Hail, Saudi Arabia

^e Central Biotechnology Services, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, UK
E-mail: deshpandes1@cardiff.ac.uk

^f Laboratory of Genetics, Biodiversity and Valorization of Bio-resources (LR11ES41), University of Monastir, Higher Institute of Biotechnology of Monastir, Avenue Tahar Haddad, BP74, 5000 Monastir, Tunisia

Abstract

The outbreak of novel coronavirus, SARS-CoV-2, has infected more than 36 million people and caused approximately 1 million deaths around the globe as of 9 October 2020. The escalating outspread of the virus and rapid rise in the number of cases require the instantaneous development of effectual drugs and vaccines. Presently, there are no approved drugs or vaccine available to treat the infection. In such scenario, one of the propitious therapeutic approaches against viral infection is to explore enzyme inhibitors amidst natural compounds, utilizing computational approaches aiming to get products with negligible side effects. In the present study, the inhibitory prospects of ilimaquinone (marine sponge metabolite) were assessed in comparison with hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir at the active binding pockets of nine different vital SARS-CoV-2 target proteins (spike receptor binding domain, RNA-dependent RNA polymerase, Nsp10, Nsp13, Nsp14, Nsp15, Nsp16, main protease, and papain-like-protease), employing an in silico molecular interaction based approach. In addition, molecular dynamics (MD) simulations of the SARS-CoV-2 papain-like protease (PLpro)–ilimaquinone complex were also carried out to calculate various structural parameters including root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (R_g) and hydrogen bond interactions. PLpro is a promising drug target, due to its imperative role in viral replication and additional function of stripping ubiquitin and interferon-stimulated gene 15 (ISG15) from host-cell proteins. In light of the possible inhibition of all vital SARS-CoV-2 target proteins, our study has emphasized the importance to study in depth ilimaquinone actions in vivo.

This article is part of the themed collection: Coronavirus articles - free to access collection

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https://doi.org/10.1039/D0RA06379G

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Paper

Submitted

22 Jul 2020

Accepted

04 Oct 2020

First published

13 Oct 2020

This article is Open Access

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RSC Adv., 2020,10, 37707-37720

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Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study

M. Surti, M. Patel, M. Adnan, A. Moin, S. A. Ashraf, A. J. Siddiqui, M. Snoussi, S. Deshpande and M. N. Reddy, RSC Adv., 2020, 10, 37707 DOI: 10.1039/D0RA06379G

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Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study

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Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study

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