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

Abstract

The new emerging coronavirus (SARS-CoV-2) has become a global health problem withvery rapid transmission from person to person, causing severe acute respiratory problems. In thecircumstance, the discovery of vaccines or drugs to eradicate or reduce the impact of the COVID19 has made it imperative to develop new approaches. In the current situation, many drugs on thedrug bank have been researched computationally, and there has not been an emphasis onsynthetic effort. We tested 42 coumarin derivatives (1a-14c) containing 14 different substituents,which are secondary metabolites of plants, and the anticoagulant Coumadin (warfarin) drug as areference by Molecular Docking calculation technique on 6LU7 main protease of the coronavirus.Optimized geometries, electron motions and energy values of all coumarins were also determinedusing the Density Functional Theory (DFT) method. The drug properties of coumarins wereestimated using the ADME-Tox test method. Coumarins formed strong interactions with HIS41,CYS145, and other amino acids in the active site of the main protease. In general, 6,7-dihydroxy3-phenylcoumarin derivatives gave relatively higher scores, and for all coumarins, biphenyl (for10a, -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 vivoexperimental research for vaccine development purposes.