In silico insight into the inhibitory effects of active antidiabetic compounds from medicinal plants against SARS-CoV-2 replication and posttranslational modification

Abstract

\n\nThe recent reemergence of the coronavirus (COVID-19) caused by the virus severe acute\nrespiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted for the search of effective treatments in forms of drugs\nand vaccines.\n\n\n\nIn this regards, we performed an in silico studies of 39 active antidiabetic compounds from medicinal plants to provide\ninsight into their possible inhibitory potentials against SARS-CoV-2 replications and post-translational modifications. Top\n12 active antidiabetic compounds with potential for dual inhibition of the replications and post-translational modifications of\nSARS-CoV-2 were analyzed.\n\n\n\nBoswellic acids, celastrol, rutin, sanguinarine, silymarin and withanolides expressed binding energy for 3-\nchymotrypsin-like protease (3CLpro) (-8.0 to -8.9 Kcal/mol), papain-like protease (PLpro) (-9.1 to -10.2 Kcal/mol) and\nRNA-dependent RNA polymerase (RdRp) (-8.5 to -9.1 Kcal/mol) which were higher than that of the reference drugs\n(Lopinavir and Remdesivir) used in this study. Sanguinarine, silymarin and withanolides are most drugable phytochemicals\namong the other following phytochemicals as they obey the Lipinski’s rule of five analyses. Sanguinarine, silymarin and\nwithanolides express moderately soluble with no hepatotoxicity, while silymarin and withanolides cannot permeate the\nblood-brain barrier and showed no Salmonella typhimurium reverse mutation assay (AMES) toxicity, unlike sanguinarine\nfrom the predictive absorption, distribution, metabolism, elimination, and toxicity (ADMET) studies.\n\n\n\nSanguinarine, silymarin and withanolides could be proposed for further experimental studies for their\ndevelopment as possible phytotherapy for the COVID-19 pandemic.\n