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. 2021 Jun 24;11(36):22398-22408.
doi: 10.1039/d1ra03937g. eCollection 2021 Jun 21.

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

Ahmed E Allam  1 , Yhiya Amen  2 , Ahmed Ashour  2 , Hamdy K Assaf  1 , Heba Ali Hassan  3 , Islam M Abdel-Rahman  4 , Ahmed M Sayed  5 , Kuniyoshi Shimizu  6
Affiliations

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

Ahmed E Allam et al. RSC Adv. .

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 of Sesamum indicum L. seeds (sesame) were led to isolation of seven known compounds, five lignan; sesamin 1, sesamolin 2, pinoresinol 3, hydroxymatairesinol 6, spicatolignan 7, together with two simple phenolic compounds; ferulic acid 4 and vanillic acid 5. All isolated compounds were evaluated in silico against 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 compound 6 has the high affinity against the three main proteins, specially towards the SARS-CoV-2 Mpro that exceeded the currently used SARS-CoV-2 Mpro inhibitor 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, compounds 1 and 2 showed also similar triple inhibitory effect against the three main proteins while compound 7 exhibited a dual inhibitory effect against SARS CoV-2 PLPro and RdRp. Further molecular dynamic simulation experiments were performed to validate these docking experiments and to calculate their binding free energies (ΔGs). Compounds 1, 2, 3, 6, and 7 showed comparable binding stability inside the active site of each enzyme with ΔG values 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.

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Conflict of interest statement

We declare that we have no conflict of interest.

Figures

Fig. 1
Fig. 1. Structure of the isolated compounds.
Fig. 2
Fig. 2. Docking results of compound 3 in the active site of SARS-CoV-2 main protease (6LU7). (A) Validation of docking procedure showing good matching between crystallized (yellow) and docked (blue) ligands. (B) Docking pose of compound 6. (C) 2D interactions of compound 6.
Fig. 3
Fig. 3. Docking results of compound 3 in the active site of SARS-CoV-2 papain-like protease (6WUU). (A) Validation of docking procedure showing good matching between crystallized and docked ligands. (B) Docking pose of compound 6. (C) 2D interactions of compound 6.
Fig. 4
Fig. 4. Docking results of compound 3 in the active site of SARS-CoV-2 RdRp (7BV2). (A) Validation of docking procedure showing good matching between crystallized and docked ligands. (B) Docking pose of compound 6. (C) 2D interactions of compound 6.
Fig. 5
Fig. 5. RMSDs of compounds 1, 2, 3, 6, and 7 inside the active sites of Mpro, PLpro, and RdRp during 50 ns of MDSs.
See this image and copyright information in PMC

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