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-