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

https://doi.org/10.1016/j.molstruc.2022.132652Get rights and content

Highlights

  • Folacin (Vitamin B9), Riboflavin (Vitamin B2), Phylloquinone oxide (Vitamin K1 oxide) and Ergocalciferol (Vitamin D2) are the structures with the best affinity in the biding site of studied enzyme: SARS-CoV-2 main protease.

  • Phylloquinone oxide and Folacin indicate that they may not fit very well in to 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, which indicates that Riboflavin (Vitamin B2) could be interesting for the antiviral treatment of COVID-19.

  • Vitamin B2 respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties and this molecule would be much cheaper and simpler than the others drugs as a therapeutic option to be tested.

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

Coronavirus
COVID-19
Vitamins
SARS-CoV-2 main protease
Molecular docking
Molecular dynamic

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