In silico, 6LU7 protein inhibition using dihydroxy-3-phenyl coumarin derivatives for SARS-CoV-2

Year 2020, Volume: 7 Issue: 3, 691 - 712, 30.10.2020

Mücahit Özdemir Baybars Köksoy Deniz Ceyhan Mustafa Bulut Bahattin Yalcin

https://doi.org/10.18596/jotcsa.753157

Cited By: 4

Abstract

The new emerging coronavirus (SARS-CoV-2) has become a global health problem with very rapid transmission from person to person, causing severe acute respiratory problems. In the circumstance, the discovery of vaccines or drugs to eradicate or reduce the impact of the COVID-19 has made it imperative to develop new approaches. In the current situation, many drugs on the drug bank have been researched computationally and the synthesis has not been emphasized much. We tested 42 coumarin derivatives (1a-14c) containing 14 different substituents, which are secondary metabolites of plants, and the anticoagulant coumadin (warfarin) drug as a reference by docking method on 6LU7 main protease. Optimized geometries, electron motions and energy values of all coumarins were also determined using the Density Functional Theory (DFT) method. Coumarins formed strong interactions with HIS41, CYS145 and other amino acids in the active site of the main protease. In general, 6,7-dihydroxy-3-phenylcoumarin derivatives gave relatively higher scores, and for all coumarins, biphenyl (for 10a, -8.6 kcal/mol; 10b, -8.3 kcal/mol; 10c -7.9 kcal/mol) and 4-trifluoromethylphenyl (for 13a, -8.1 kcal/mol; 13b, -8.1 kcal/mol; 13c -8.3 kcal/mol) substituted coumarin had the highest score. The coumarins data reported in this study serves as a stepping stone for in vitro and in vivo experimental research for vaccine development purposes.

Keywords

COVID-19 main protease, SARS-CoV-2, Molecular docking, Drug design, Coumarins

Thanks

The numerical calculations reported in this paper were fully performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).

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