Inhibitory potentials of ivermectin, nafamostat, and camostat on spike protein and some nonstructural proteins of SARS-CoV-2: Virtual screening approach

Abstract

The search for potent oral drugs either through synthetic routes or by drug repurposing for combating the dreaded covid-19 virus is still ongoing. The coronavirus spike glycoprotein and several other non-structural proteins play crucial roles in the replication and transmission of this virus. Recent research have identified ivermectin, nafamostat, and camostat as promising drug inhibitors of SARS-CoV-2 target proteins. The broad-spectrum inhibitory action of ivermectin, nafamostat, and camostat on the spike glycoprotein and some non-structural proteins of this virus was studied in silico. The spike glycoprotein, nsp3, nsp5, nsp9, nsp10, nsp13, and nsp16 were selected for this study and were downloaded from the protein data bank. Flexible docking procedure implemented in Auto Dock Vina module was deployed for the docking procedure of the drugs with the protein receptors. Although ivermectin had the best inhibitory action on the viral spike protein and nsp10, nafamostat was identified as the compound with the best broad-spectrum activity on this virus, having the highest binding affinity values of – 9.4kcal/mol, – 7.9 Kcal/mol, – 6.1 Kcal/mol, – 8.0 Kcal/mol, and – 8.7 Kcal/mol for nsp3, nsp5, nsp9, nsp13, and nsp16 respectively. This drug, in combination with ivermectin could therefore be explored further as potential compounds that could be modified to curb the menace of the covid-19 pandemic.