In silico detection of potential inhibitors from vitamins and their derivatives compounds against SARS-CoV-2 main protease by using molecular docking, molecular dynamic simulation and ADMET profiling

Assia Belhassan; Samir Chtita; Hanane Zaki; Marwa Alaqarbeh; Nada Alsakhen; Firas Almohtaseb; Tahar Lakhlifi; Mohammed Bouachrine

doi:10.1016/j.molstruc.2022.132652

In silico detection of potential inhibitors from vitamins and their derivatives compounds against SARS-CoV-2 main protease by using molecular docking, molecular dynamic simulation and ADMET profiling

J Mol Struct. 2022 Jun 15:1258:132652. doi: 10.1016/j.molstruc.2022.132652. Epub 2022 Feb 18.

Authors

Assia Belhassan¹, Samir Chtita², Hanane Zaki³, Marwa Alaqarbeh⁴, Nada Alsakhen⁵, Firas Almohtaseb⁶, Tahar Lakhlifi¹, Mohammed Bouachrine^{1

3}

Affiliations

¹ Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco.
² Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca 7955, Morocco.
³ EST Khenifra, Sultan Moulay Sliman University, Benimellal, Morocco.
⁴ National Agricultural Research Center, Al‑Baqa 19381, Jordan.
⁵ Department of Chemistry, Faculty of Science, The Hashemite University, Zarqa, Jordan.
⁶ Institute of Water and Environmental Management, University of Debrecen, Egyetemtér 1, Debrecen 4032 Hungary.

Abstract

COVID-19 is a new infectious disease caused by SARS-COV-2 virus of the coronavirus Family. The identification of drugs against this serious infection is a significant requirement due to the rapid rise in the positive cases and deaths around the world. With this concept, a molecular docking analysis for vitamins and their derivatives (28 molecules) with the active site of SARS-CoV-2 main protease was carried out. The results of molecular docking indicate that the structures with best binding energy in the binding site of the studied enzyme (lowest energy level) are observed for the compounds; Folacin, Riboflavin, and Phylloquinone oxide (Vitamin K1 oxide). A Molecular Dynamic simulation was carried out to study the binding stability for the selected vitamins with the active site of SARS-CoV-2 main protease enzyme. Molecular Dynamic shows that Phylloquinone oxide and Folacin are quite unstable in binding to SARS-CoV-2 main protease, while the Riboflavin is comparatively rigid. The higher fluctuations in Phylloquinone oxide and Folacin indicate that they may not fit very well into the binding site. As expected, the Phylloquinone oxide exhibits small number of H-bonds with protein and Folacin does not form a good interaction with protein. Riboflavin exhibits the highest number of Hydrogen bonds and forms consistent interactions with protein. Additionally, this molecule respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties which indicates that Riboflavin (Vitamin B2) could be interesting for the antiviral treatment of COVID-19.

Keywords: COVID-19; Coronavirus; Molecular docking; Molecular dynamic; SARS-CoV-2 main protease; Vitamins.