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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Identification of Novel Drug Candidates for the Inhibition of Catalytic Cleavage Activity of Coronavirus 3CL-like Protease Enzyme

Author(s): Arun Bahadur Gurung*, Khalid Mashay Al-Anazi, Mohammad Ajmal Ali, Joongku Lee and Mohammad Abul Farah*

Volume 23, Issue 7, 2022

Published on: 03 August, 2021

Page: [959 - 969] Pages: 11

DOI: 10.2174/1389201022666210604150041

Price: $65

Abstract

Background: There has been tremendous pressure on healthcare facilities globally due to the recent emergence of novel coronavirus infection known as COVID-19 and its rapid spread across the continents. The lack of effective therapeutics for the management of the pandemic calls for the discovery of new drugs and vaccines.

Objective: In the present study, a chemical library was screened for molecules against three coronavirus 3CL-like protease enzymes (SARS-CoV-2 3CLpro, SARS-CoV 3CLpro and MERS-CoV 3CLpro), which are a key player in the viral replication cycle.

Methods: Extensive computational methods such as virtual screening and molecular docking were employed in this study.

Results: Two lead molecules, ZINC08825480 (4-bromo-N'-{(E)-[1-phenyl-3-(pyridin-3-yl)-1H-pyrazol- 4-yl]methylidene}benzene-1-sulfonohydrazide) and ZINC72009942 (N-[[2-[[(3S)-3-methyl-1-piperidyl] methyl]phenyl]methyl]-6-oxo-1-(p-tolyl)-4,5-dihydro-1,2,4-triazine-3-carboxamide), were identified with better affinity with the three target enzymes as compared to the approved antiviral drugs. Both the lead molecules possessed favorable drug-like properties, fit well into the active site pocket close to His- Cys dyad and showed a good number of hydrogen bonds with the backbone as well as side chains of key amino acid residues.

Conclusion: Thus, the present study offers two novel chemical entities against coronavirus infections which can be validated through various biological assays.

Keywords: 3CL-like protease, main protease, SARS-CoV-2 3CLpro , SARS-CoV 3CLpro, MERS-CoV 3CLpro, antiviral drugs.

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