Targeting SARS-CoV-2 Spike Protein/ACE2 Protein-Protein Interactions: a Computational Study

The spike glycoprotein (S) of the SARS-CoV-2 virussurface plays a key role in receptor binding and virus entry.The S protein uses the angiotensin converting enzyme(ACE2) for entry into the host cell and binding to ACE2occurs at the receptor binding domain (RBD) of the Sprotein. Therefore, the protein-protein interactions (PPIs)between the SARS-CoV-2 RBD and human ACE2, could beattractive therapeutic targets for drug discovery approachesdesigned to inhibit the entry of SARS-CoV-2 into the hostcells. Herein, with the support of machine learningapproaches, we report structure-based virtual screening asan effective strategy to discover PPIs inhibitors from ZINCdatabase. The proposed computational protocol led to theidentification of a promising scaffold which was selected forsubsequent binding mode analysis and that can represent auseful starting point for the development of new treatmentsof the SARS-CoV-2 infection.