Molecular Docking Studies of Boron‐Containing Compounds as Dual Inhibitors of SARS‐Cov‐2 Spike Receptor Binding Domain/ACE2 Complex and Main Protease and ADMET Investigations

Abstract The severe acute respiratory syndrome SARS‐CoV‐2 is the causative agent of COVID‐19. Preventing binding of SARS‐CoV‐2 Spike glycoprotein to human ACE2 enzyme and inhibition of M PRO enzyme are still attractive drug targets for treatment of COVID‐19 infection. Boron atom‐containing compounds show anticancer, antibacterial, antiviral, antifungal, antiparasitic, anti‐inflammatory, antituberculosis, anti‐dermatophytic and anti‐fertility activities. In the current study, the ADMET properties of ligands were calculated by the aim of SwissADME and pkCSM pharmacokinetics web tools. The results revealed that the ligands meet drug‐likeness properties. Furthermore, we have performed molecular docking study of boron containing dioxaborepine and oxadiazaborole derivatives to investigate binding properties of ligands against SARS‐CoV‐2 Spike glycoprotein/ACE2 complex and inhibition of M PRO enzyme. Through the ligands a derivative of dioxaborepine showed best binding score against SARS‐CoV‐2 Spike glycoprotein/ACE2 complex with a binding score of −8.93 kcal/mol and a oxadiazaborole derivative exhibited a binding score value of −8.36 kcal which is the best binding ligand to the M PRO enzyme binding site. The analysis of binding poses of ligands and ligand‐residue interactions of the systems revealed that dioxaborepines and oxadiazaboroles could have block binding of Spike glycoprotein to human ACE2 enzyme and could have inhibition effects on M PRO enzyme.