Targeting SARS-CoV-2 Spike Protein/ACE2 Protein-Protein Interactions: a Computational Study.
Davide PirolliBenedetta RighinoMaria Cristina De RosaPublished in: Molecular informatics (2021)
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.
Keyphrases
- sars cov
- angiotensin converting enzyme
- angiotensin ii
- respiratory syndrome coronavirus
- binding protein
- drug discovery
- machine learning
- protein protein
- amino acid
- induced apoptosis
- endothelial cells
- dna binding
- randomized controlled trial
- single cell
- oxidative stress
- artificial intelligence
- cell cycle arrest
- small molecule
- induced pluripotent stem cells
- deep learning
- cell proliferation
- bioinformatics analysis
- pi k akt