Molecular Dynamics Simulation, QSAR, DFT, Molecular Docking, ADMET, and Synthesis of Ethyl 3-((5-Bromopyridin-2-yl)Imino)Butanoate Analogues as Potential Inhibitors of SARS-CoV-2

Structural modifications of ethyl-3-((5-bromopyridin-2-yl)imino)butanoate ester enhances its biological activities. In the present work, the synthesis of a Schiff base by reacting 2-amino-5-bromo pyridine and ethyl acetoacetate was reported. Electronic properties were investigated by the computational method of density functional theory (DFT). The pass prediction score supported anti-viral efficacy which satisfied the Lipiniski rule and overall HOMO-LUMO. The most important part of this investigation was docking study which revealed that the ligands L07 has nearly efficacy to standard drugs and maximum docking score was found against Alpha variant (7EKF) at −6.7 kcal/mol, Beta variant (7ekg) at −6.2 kcal/mol, Gamma variant (7EKC) at −6.5 kcal/mol, Beta variant (7ekg) at −6.2 kcal/mol, SARS-CoV-2 Gamma variant (7EKC) at −6.2 kcal/mol, Delta variant (7V8B) at −6.1 kcal/mol and Omicron variant (7T9J) at −6.3 kcal/mol. Finally, molecular dynamics study was performed to determine the stability and it was reported that the molecules L07 has better stability to be an oral drug against the different variant of SARS-CoV-2 viral pathogen.