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

The spike glycoprotein (S) of the SARS-CoV-2 virus
surface 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 ACE2
occurs at the receptor binding domain (RBD) of the S
protein. Therefore, the protein-protein interactions (PPIs)
between the SARS-CoV-2 RBD and human ACE2, could be
attractive therapeutic targets for drug discovery approaches
designed to inhibit the entry of SARS-CoV-2 into the host
cells. Herein, with the support of machine learning
approaches, we report structure-based virtual screening as
an effective strategy to discover PPIs inhibitors from ZINC
database. The proposed computational protocol led to the
identification of a promising scaffold which was selected for
subsequent binding mode analysis and that can represent a
useful starting point for the development of new treatments
of the SARS-CoV-2 infection.