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
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