Molecular modeling of the interaction of ligands with ACE2–SARS-CoV-2 spike protein complex

Isaac-Lam, Meden F.

COVID-19 is a new communicable disease with a widespread outbreak that affects all populations worldwide triggering a rush of scientific interest in coronavirus research globally. In silico molecular docking experiment was utilized to determine interactions of available compounds with SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) complex. Chimera and AutoDock Vina were used for protein–ligand interaction structural analysis. Ligands were chosen based on the known characteristics and indications of the drugs as ACE inhibitors (captopril, enalapril, quinapril, moexipril, benazepril, ramipril, perindopril, zofenopril, fosinopril), as ACE2 blockers (losartan, olmesartan), as blood thinning agent (clopidogrel), as cholesterol-lowering prescriptions (simvastatin, atorvastatin), repurposed medications (dexamethasone, hydroxychloroquine, chloroquine), and as investigational drug (remdesivir). Experimental ACE/ACE2 inhibitors are also included: Sigma ACEI, N-(2-aminoethyl)-1-aziridine-ethanamine (NAAE), nicotianamine (NAM), and MLN-4760 (ACE2 inhibitor). The best docked conformations were all located in the ACE2 protein, 50% docked at the interface with lower scores and only clopidogrel and hydroxychloroquine docked at the spike protein. Captopril, moexipril, benazepril, fosinopril, losartan, remdesivir, Sigma ACEI, NAA, and NAM interacted and docked at the interface of ACE2 and SARS-CoV-2 spike protein complex. This may have significant implication in enhancing our understanding of the mechanism to hinder viral entry into the host organism during infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00114-w.