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

(E-pub Ahead of Print)

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

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


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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 aim 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 resulted from VS were myricetin (1) available in Alium cepa, Mentha piperita, α- hydroxyhydrocaffeic acid (2) available in M. Piperita and luteolin (3) available in M. Piperita, Curcuma longa, A. cepa, 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 modelling of protein. Here, we used the recently uploaded X-ray crystal structure of PLpro (PDB ID: 6WX4) with the 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 home remedy after in-vitro study.

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

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(E-pub Ahead of Print)
DOI: 10.2174/2666796701999201203211330

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