Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches.

Autor: Bhowmick S; Department of Chemical Technology, University of Calcutta, 92, A.P.C. Road, Kolkata, 700009, India., Saha A; Department of Chemical Technology, University of Calcutta, 92, A.P.C. Road, Kolkata, 700009, India. Electronic address: achintya_saha@yahoo.com., AlFaris NA; Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, P. O. Box 84428, Riyadh, 11671, Saudi Arabia., ALTamimi JZ; Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, P. O. Box 84428, Riyadh, 11671, Saudi Arabia., ALOthman ZA; Department of Chemistry, P.O. Box 2455, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia., Aldayel TS; Nutrition and Food Science, Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, P. O. Box 84428, Riyadh, 11671, Saudi Arabia., Wabaidur SM; Department of Chemistry, P.O. Box 2455, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia., Islam MA; Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: ataul.islam80@gmail.com.
Jazyk: angličtina
Zdroj: Journal of molecular graphics & modelling [J Mol Graph Model] 2022 Mar; Vol. 111, pp. 108113. Date of Electronic Publication: 2021 Dec 21.
DOI: 10.1016/j.jmgm.2021.108113
Abstrakt: The current ongoing pandemic of COVID-19 urges immediate treatment measures for controlling the highly contagious SARS-CoV-2 infections. The papain-like protease (PLpro), which is released from nsp3, is presently being evaluated as a significant anti-viral drug target for COVID-19 therapy development. Particularly, PLpro is implicated in the cleavage of viral polyproteins and antagonizes the host innate immune response through its deubiquitinating and deISGylating actions, thus making it a high-profile antiviral therapeutic target. The present study reports a few specific food compounds that can bind tightly with the SARS-CoV-2 PLpro protein identified through extensive computational screening techniques. Precisely, extensive advanced computational approaches combining target-based virtual screening, particularly employing sub-structure based similarity search, molecular docking, molecular dynamics (MD) simulations, and MM-GBSA based binding free energy calculations have been employed for the identification of the most promising food compounds with substantial functional implications as SARS-CoV-2 PLpro protein inhibitors/modulators. Observations from the present research investigation also provide a deeper understanding of the binding modes of the proposed four food compounds with SARS-CoV-2 PLpro protein. In docking analyses, all compounds have established essential inter-molecular interaction profiles at the active site cavity of the SARS-CoV-2 PLpro protein. Similarly, the long-range 100 ns conventional MD simulation studies also provided an in-depth understanding of probable interactions and dynamic behaviour of the SARS-CoV-2 PLpro protein-food compound complexes. Binding free energies of all molecular systems revealed a strong interaction affinity of food compounds towards the SARS-CoV-2 PLpro protein. Moreover, clear-cut comparative analyses against the known standard inhibitor also suggest that proposed food compounds may act as potential active chemical entities for modulating the action of the SARS-CoV-2 PLpro protein.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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