In Silico Identification of Potential Inhibitors of SARS-CoV-2 Papain-like Protease From Natural Sources: A Natural Weapon to Fight COVID-19

Author(s): Bimal Debnath, Pradip Debnath, Rajat Ghosh, Sudhan Debnath*

Journal Name: Coronaviruses
The World's First International Journal Dedicated to Coronaviruses

Volume 2 , Issue 8 , 2021


Article ID: e260721188689
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Abstract:

Background: The rapid spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) globally has created unprecedented health care and economic crisis. The ever-increasing death toll highlights an urgent need for the development of specific antiviral to combat Novel Coronavirus Disease 2019 (COVID-19).

Objective: In the present study, we aimed to identify potential SARS-CoV-2 papain-like protease inhibitors from regularly used spices.

Methods: A structure-based virtual screening (VS) of our in-house databank of 1152 compounds was employed to identify small molecule inhibitors of SARS-CoV-2 papain-like protease (PLpro), which are important protease for virus replication. The databank was built of the compounds from ten spices and two medicinal plants.

Results: The top three potential hits that resulted from VS were myricetin (1) available in Alium cepa and Mentha piperita; α-hydroxyhydrocaffeic acid (2) available in M. Piperita; and luteolin (3) available in M. Piperita, Curcuma longa, A. cepa, and Trigonella foenum-graecum, which showed fair binding affinity to PLpro of SARS-CoV-2 compared to known SARS-CoV PLpro inhibitors. The predicted Absorption, Distribution, Metabolism, and Excretion (ADME) properties of the selected hits showed that all are drug-like. The compounds bind to biologically critical regions of the target protein, indicating their potential to inhibit the functionality of this component.

Conclusion: There are only a few reports available in the literature on the in-silico identification of PLpro inhibitors and most of them used homology modeling of protein. Here, we used the recently uploaded X-ray crystal structure of PLpro (PDB ID: 6WX4) with a well-defined active site. Our computational approach has resulted in the identification of effective inhibitors of SARS-CoV-2PLpro. The reported edible spices may be useful against COVID-19 as a home remedy after an in- -vitro study.

Keywords: COVID-19, SARS-CoV-2, virtual screening, ADME, papain-like protease, spices.

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Article Details

VOLUME: 2
ISSUE: 8
Year: 2021
Published on: 03 December, 2020
Article ID: e260721188689
Pages: 12
DOI: 10.2174/2666796701999201203211330

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