In silico study of natural compounds from sesame against COVID-19 by targeting Mpro, PLpro and RdRp

Abstract

Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. Natural products as sesame were reported to exhibit potential to protect from COVID-19 disease. In our study, the total methanolic extract ofSesamum indicumL. seeds (sesame) were led to isolation of seven known compounds, five lignan; sesamin1, sesamolin2, pinoresinol3, hydroxymatairesinol6, spicatolignan7, together with two simple phenolic compounds; ferulic acid4and vanillic acid5. All isolated compounds were evaluatedin silicoagainst three important SARS-CoV-2 protein targets; main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) which possessed crucial role in replication and proliferation of the virus inside the human cell. The results revealed that compound6has the high affinity against the three main proteins, specially towards the SARS-CoV-2 Mprothat exceeded the currently used SARS-CoV-2 Mproinhibitor darunavir as well as, exhibiting a similar binding energy at SARS CoV-2 PLpro when compared with the co-crystallized ligand. This activity continued to include the RdRp as it displayed a comparable docking score with remdesivir. Inferiorly, compounds1and2showed also similar triple inhibitory effect against the three main proteins while compound7exhibited a dual inhibitory effect against SARS CoV-2 PLProand RdRp. Further molecular dynamic simulation experiments were performed to validate these docking experiments and to calculate their binding free energies (ΔGs). Compounds1,2,3,6, and7showed comparable binding stability inside the active site of each enzyme with ΔGvalues ranged from −4.9 to −8.8 kcal mol−1. All the compounds were investigated for their ADME and drug likeness properties, which showed acceptable ADME properties and obeying Lipinski's rule of five parameters. It can be concluded that the isolated compounds from sesame lignans could be an alternative source for the development of new natural leads against COVID-19.