Issue 8, 2021

Ligand-based design, molecular dynamics and ADMET studies of suggested SARS-CoV-2 Mpro inhibitors

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been the choice of recent studies worldwide to control its pandemic. Given the similarity with the earlier SARS-CoV, it is possible to use the previously reported inhibitors to develop a new treatment for the current attack of SARS-CoV-2. This study used the formerly published SARS-CoV Mpro small-molecule protease inhibitors to develop a pharmacophore model in order to design new ligands. Several strategies and scaffolds were evaluated in silico giving rise to ten newly designed compounds. Molecular docking and dynamics simulations were performed on Mpro enzyme in its active site to evaluate the newly designed ligands I–X. The results obtained from this work showed that compounds III–VI had a better molecular docking score than the co-crystallized ligand baicalein (3WL) giving −5.99, −5.94, −6.31, −6.56 and −5.74 kcal mol−1, respectively. Moreover, they could bind to the Mpro binding site better than I, II and VII–X. The most promising chromen-2-one based compounds V–VI had sufficiently acceptable physicochemical and ADMET properties to be considered new leads for further investigations. This new understanding should help to improve predictions of the impact of new treatments on COVID-19.

Graphical abstract: Ligand-based design, molecular dynamics and ADMET studies of suggested SARS-CoV-2 Mpro inhibitors

Article information

Article type
Paper
Submitted
01 Dec 2020
Accepted
31 Dec 2020
First published
22 Jan 2021
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2021,11, 4523-4538

Ligand-based design, molecular dynamics and ADMET studies of suggested SARS-CoV-2 Mpro inhibitors

N. M. Mohamed, E. M. H. Ali and A. M. AboulMagd, RSC Adv., 2021, 11, 4523 DOI: 10.1039/D0RA10141A

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