Background: The recent reemergence of the coronavirus (COVID-19) caused by the virus severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted for the search of effective treatments in forms of drugs
Aim: In this regards, we performed an in silico studies of 39 active antidiabetic compounds from 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 that of the reference drugs
(Lopinavir and Remdesivir) used in this study. Sanguinarine, silymarin and withanolides are most drugable phytochemicals
among the other following phytochemicals as they obey the Lipinski’s rule of five analyses. Sanguinarine, silymarin and
withanolides express moderately soluble with no hepatotoxicity, while silymarin and withanolides cannot 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.