s In Silico Insight into the Inhibitory Effects of Active Antidiabetic Compounds from Medicinal Plants Against SARS-CoV-2 Replication and Posttranslational Modification

Background: The recent reemergence of the coronavirus (COVID-19) caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted the search for effective treatments in the forms of drugs and vaccines. Aim: In this regard, we performed an in silico study on 39 active antidiabetic compounds of medicinal plants to provide insight into their possible inhibitory potentials against SARS-CoV-2 replications and post-translational modifications. Top 12 active antidiabetic compounds with potential for dual inhibition of the replications and post-translational modifications of SARS-CoV-2 were analyzed. Results: Boswellic acids, celastrol, rutin, sanguinarine, silymarin, and withanolides expressed binding energy for 3-chymotrypsin-like protease (3CLpro) (-8.0 to -8.9 Kcal/mol), papain-like protease (PLpro) (-9.1 to -10.2 Kcal/mol), and RNA-dependent RNA polymerase (RdRp) (-8.5 to -9.1 Kcal/- mol) which were higher than the reference drugs (Lopinavir and Remdesivir) used in this study. Sanguinarine, silymarin, and withanolides are the most druggable phytochemicals among other phytochemicals as they follow Lipinski’s rule of five analyses. Sanguinarine, silymarin, and withanolides expressed moderate solubility with no hepatotoxicity, while silymarin and withanolides could not permeate the blood-brain barrier and showed no Salmonella typhimurium reverse mutation assay (AMES) toxicity, unlike sanguinarine from the predictive absorption, distribution, metabolism, elimination, and toxicity (ADMET) studies. Conclusion: Sanguinarine, silymarin, and withanolides could be proposed for further experimental studies for their development as possible phytotherapy for the COVID-19 pandemic.