Dietary polyphenols mitigate SARS-CoV-2 main protease (Mpro)–Molecular dynamics, molecular mechanics, and density functional theory investigations

•Ellagic acid and Kievitone are promising inhibitors of SARSCOV-2 main protease.•Both compounds have higher potentials to disrupt the His41 and Cys145 crucial residues of Mpro than Remdesivir.•Functinal foods endowed with Kievitone and Ellagic acid may be functional in the treatment/Management of CO...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of molecular structure Vol. 1250; p. 131879
Main Authors:	Adelusi, Temitope Isaac, Oyedele, Abdul-Quddus Kehinde, Monday, Ojo Emmanuel, Boyenle, Ibrahim Damilare, Idris, Mukhtar Oluwaseun, Ogunlana, Abdeen Tunde, Ayoola, Ashiru Mojeed, Fatoki, John Olabode, Kolawole, Oladipo Elijah, David, Kehinde Busuyi, Olayemi, Akintola Adebola
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 15-02-2022
Subjects:	Molecular docking Molecular dynamics Molecular mechanics Quantum mechanics SARS-COV2 Mpro inhibitors Molecular mechanics ORF Mpro Quantum mechanics Molecular dynamics HOMO LUMO MM-PBSA ADMET GROMACS Molecular docking SARS-COV2 Mpro inhibitors HOMO, highest occupied molecular orbital LUMO, lowest unoccupied molecular orbital MM-PBSA, molecular mechanics Poisson–Boltzmann Surface Area GROMACS, GROningen MAchine for chemical simulations ADMET, absorption, distribution, metabolism, excretion, and toxicity Mpro, main protease ORF, open reading frame
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	•Ellagic acid and Kievitone are promising inhibitors of SARSCOV-2 main protease.•Both compounds have higher potentials to disrupt the His41 and Cys145 crucial residues of Mpro than Remdesivir.•Functinal foods endowed with Kievitone and Ellagic acid may be functional in the treatment/Management of COVID-19. The recent evolution of the SARS-like Coronavirus has ravaged the world. The deadly virus has claimed over millions of lives across the world and hence highlights the need to develop effective therapeutic drugs to contain the disease posed by this parasite. In this study, the inhibitory potential of fifty (50) dietary polyphenols against Coronavirus (SARS-CoV-2) main protease (Mpro) was conducted using the Autodock Vina Molecular docking tool. In the virtual screening process, the binding affinity of Remdesivir (-7.7 kcal/mol) currently used to treat COVID-19 patients was set as the cut-off value to screen out less probable inhibitors. Ellagic acid, Kievitone, and Punicalin were the only promising ligands with binding affinities (-8.9 kcal/mol, -8.0 kcal/mol and -7.9 kcal/mol respectively) lower than the set cut-off value. Furthermore, we validated Ellagic acid and Kievitone efficacy by subjecting them to molecular dynamics simulation and further stability was assessed at the molecular mechanics and quantum levels. The overall analysis indicates both compounds demonstrate higher stability and inhibitory potential to bind to the crucial His41 and Cys145 catalytic dyad of Mpro than the standard drug. However, further analysis of punicalin after evaluating its docking score was not conducted as the ligand pharmacokinetics properties suggests it could pose serious adverse effect to the health of participants in clinical trials. Hence, we employed a more safe approach by filtering out the compound during this study. Conclusively, while Ellagic acid and kievitone polyphenolic compounds have been demonstrated to be promising under this in silico research, further studies are needed to substantiate their clinical relevance. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-2860 1872-8014
DOI:	10.1016/j.molstruc.2021.131879