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Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19.

Authors
  • Bhati, Shipra1
  • 1 Department of Chemistry, The Oxford College of Engineering, Bommanhalli, Bangalore, 560068, Karnataka, India. , (India)
Type
Published Article
Journal
Heliyon
Publisher
Elsevier
Publication Date
Nov 01, 2020
Volume
6
Issue
11
Identifiers
DOI: 10.1016/j.heliyon.2020.e05558
PMID: 33251371
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via -NHCO- linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19. © 2020 Published by Elsevier Ltd.

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