Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

21 April 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (Mpro) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against Mpro, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of Mpro with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of Mpro. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to Mpro, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.


COVID-19, SARS-CoV2, alchemical simulations, nonequilibrium, hydroxychloroquine, ligand design, main protease, 3CLpro, PLpro, RdRp, Jarzynski theorem
Main protease (Mpro)
Molecular docking analysis


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