Unexpected efficient one-pot synthesis, DFT calculations, and docking study of new 4-hydroxy-2H-chromen-2-one derivatives predicted to target SARS-CoV-2 spike protein

Abstract

A series of new heterocyclic systems derivatives of coumarin were prepared, and their chemical structures were well confirmed by 1H/13C NMR analyses. On the other hand, Spike-RDB protein of SARS-CoV-2 virus is one of the most crucial investigated targets in the field of combat against Covid-19 pandemic, due to its decisive role in the infection process by facilitating viral entry into the human host cells. In this context, Molecular docking experiments were carried out to identify the possible binding affinity of the synthesized compounds in the binding domain of Omicron S-RBD–hACE2 complex. The outputs revealed that some compounds showed highest binding affinities even than the control drugs used in this study. It was found that certain crucial residues like Glu37, His34, and Lys353, responsible for the binding of the spike protein to its hACE2 receptor, established significant hydrogen and electrostatic interactions with the ligands.