In Silico Insight into the Inhibitory Effects of Active Antidiabetic Compounds from Medicinal Plants Against SARS-CoV-2 Replication and Post-translational 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(s): 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 ana-lyzed. Result(s): 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 phy-tochemicals as they follow Lipinski's rule of five analyses. Sanguinarine, silymarin, and withano-lides expressed moderate solubility with no hepatotoxicity, while silymarin and withanolides could not permeate the blood-brain barrier and showed no Salmonella typhimurium reverse mutation as-say (AMES) toxicity, unlike sanguinarine from the predictive absorption, distribution, metabolism, elimination, and toxicity (ADMET) studies. Conclusion(s): Sanguinarine, silymarin, and withanolides could be proposed for further experimental studies for their development as possible phytotherapy for the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

In silico investigation and identification of bioactive compounds from medicinal plants as potential inhibitors against SARS-CoV-2 cellular entry

The present study conducted an in silico investigation and identifications of bioactive compounds from medicinal plants against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cellular entry. Thirty nine (39) bioactive compounds with evidence of in vitro or in vivo antidiabetic activities from medicinal plants were utilized in order to provide insight about their possible inhibitory potentials against SARS-CoV-2 cellular entry. Results from this study showed that silymarin, sanguinarine, withanolides, boswellic acids, fisetin, celastrol, neferine, ursolic acid, rutin, gambogic acid, quercetin, and luteolin expressed multiple binding capacity against nucleocapsid dimerization domain (−10.7 to −8.4kcal/mol), spike's protein binding domain (−10.0 to −8.1kcal/mol), and spike receptor-binding domain (−10.8 to −9.0kcal/mol) compared to lopinavir and remdesivir which were used as reference compounds in the study. However, withanolides, fisetin, luteolin, sanguinarine, and silymarin are most druggable phytochemicals as they obey the Lipinski's rule of five analyses with no signs of in silico predictory toxicity. Thus, they are recommended for further studies for the development of phytotherapy formulation to combat SARS-CoV-2 disease. © 2022 Elsevier Inc. All rights reserved.