Identification of pyrazole derivatives of usnic acid as novel inhibitor of SARS-CoV-2 main protease through virtual screening approaches

Roney, Miah and Singh, Gagandeep and Huq, A.K.M. Moyeenul and Forid, Md Shaekh and Wan Ishak, Wan Maznah and Rullah, Kamal and Mohd Aluwi, Mohd Fadhlizil Fasihi and Tajuddin, Saiful Nizam (2023) Identification of pyrazole derivatives of usnic acid as novel inhibitor of SARS-CoV-2 main protease through virtual screening approaches. Molecular Biotechnology. pp. 1-11. ISSN 1073-6085 E-ISSN 1559-0305

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Abstract

The infection produced by the SARS-CoV-2 virus remains a significant health crisis worldwide. The lack of specific medications for COVID-19 necessitates a concerted effort to find the much-desired therapies for this condition. The main protease (Mpro) of SARS-CoV-2 is a promising target, vital for virus replication and transcription. In this study, fifty pyrazole derivatives were tested for their pharmacokinetics and drugability, resulting in eight hit compounds. Subsequent molecular docking simulations on SARS-CoV-2 main protease afforded two lead compounds with strong affinity at the active site. Additionally, the molecular dynamics (MD) simulations of lead compounds (17 and 39), along with binding free energy calculations, were accomplished to validate the stability of the docked complexes and the binding poses achieved in docking experiments. Based on these findings, compound 17 and 39, with their favorable projected pharmacokinetics and pharmacological characteristics, are the proposed potential antiviral candidates which require further investigation to be used as anti-SARS-CoV-2 medication.

Item Type:	Article (Journal)
Uncontrolled Keywords:	SARS-CoV-2 · Pyrazole derivatives of Usnic acid · ADMET · Drug-likeness · Docking · Molecular dynamics simulation
Subjects:	R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User:	Dr Kamal Rullah
Date Deposited:	22 Mar 2023 15:08
Last Modified:	22 Mar 2023 15:08
URI:	http://irep.iium.edu.my/id/eprint/104171

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