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. 2022 Jun:145:105452.
doi: 10.1016/j.compbiomed.2022.105452. Epub 2022 Mar 26.

Multidimensional in silico strategy for identification of natural polyphenols-based SARS-CoV-2 main protease (Mpro) inhibitors to unveil a hope against COVID-19

Şevki Adem  1 , Volkan Eyupoglu  2 , Ibrahim M Ibrahim  3 , Iqra Sarfraz  4 , Azhar Rasul  5 , Muhammad Ali  6 , Abdo A Elfiky  7
Affiliations

Multidimensional in silico strategy for identification of natural polyphenols-based SARS-CoV-2 main protease (Mpro) inhibitors to unveil a hope against COVID-19

Şevki Adem et al. Comput Biol Med. 2022 Jun.

Abstract

SARS-CoV-2, a rapidly spreading new strain of human coronavirus, has affected almost all the countries around the world. The lack of specific drugs against SARS-CoV-2 is a significant hurdle towards the successful treatment of COVID-19. Thus, there is an urgent need to boost up research for the development of effective therapeutics against COVID-19. In the current study, we investigated the efficacy of 81 medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro by using various in silico techniques. The interaction affinities of polyphenolic compounds towards SARS-CoV-2 Mpro was assessed via intramolecular (by Quantum Mechanic), intermolecular (by Molecular Docking), and spatial (by Molecular Dynamic) simulations. Our obtained result demonstrate that Hesperidin, rutin, diosmin, and apiin are most effective compounds agents against SARS-CoV-2 Mpro as compared to Nelfinavir (positive control). This study will hopefully pave a way for advanced experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19.

Keywords: COVID-19; Flavonoids; Molecular docking; Molecular dynamics simulation; Quantum mechanic; SARS CoV-2 M(pro).

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Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
MolDock docking experiment (A) MolDock scores calculated for the best 24 natural polyphenols and Nilfinavir against the SARS-CoV-2 Mpro. (B) Summary of the in silico based screening of natural product library and identification of potential natural inhibitors of SARS-CoV-2 Mpro.
Fig. 2
Fig. 2
Interactions of hesperidin and COVID-19 virus Mpro.
Fig. 3
Fig. 3
Interactions of rutin and COVID-19 virus Mpro.
Fig. 4
Fig. 4
Interactions of apiin and COVID-19 virus Mpro.
Fig. 5
Fig. 5
Interactions of diosmin and COVID-19 virus Mpro.
Fig. 6
Fig. 6
3D plots frontier orbital energies using DFT method for hesperidin, rutin, diosmin, apiin, and nelfinavir compounds.
Fig. 7
Fig. 7
Electrophilic surface-based electrostatic potential map containing the Fukui surfaces.
Fig. 8
Fig. 8
Molecular Dynamics Simulation of SARS-CoV-2 Mpro. (A) RMSD (in Å) in blue, RoG (Å) in red, Number of H-bonds in yellow, and SASA (in Å2) in gray versus time in ns. (B) Histogram of the four parameters mentioned in A with the same color code. (C) The per-residue RMSF of SARS-CoV-2 Mpro with the protein structure represented in the green cartoon. The most movable parts are marked in the RMSF chart and the protein structure (the encircled blue helix and yellow coil).
See this image and copyright information in PMC

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