In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants

Despite the rigorous global efforts to control SARS-CoV-2 transmission, it continues pose a serious threat humans with frequent emergence of new variants. Thus, robust therapeutics combat virus are desperate need. The spike (S) protein is an important target as mediates entry inside host cells, which initiated by binding receptor-binding domain (RBD) its cognate receptor, angiotensin-converting enzyme 2 (ACE-2). Herein, inhibition potential several naturally occurring coumarins was investigated against proteins variants using computational approaches. Molecular docking studies revealed 26 better energies than reference ligands, molnupiravir and ceftazidime, S-RBD omicron variant. top 10 best-docked were further analyzed understand their interactions other (wild-type, Alpha, Beta, Gamma, Delta), these also demonstrated decent energies. Physicochemical, QSAR, pharmacokinetics analyses wedelolactone best inhibitor ideal Lipinski’s drug-likeness optimal ADMET properties. Furthermore, coarse-grained molecular dynamics (MD) simulation protein-wedelolactone complexes validated stable in respective pockets. As outcome, could be utilized develop potent drug candidate COVID-19 blocking viral into cell.