Rational approaches to discover SARS-CoV-2/ACE2 interaction inhibitors: from pharmacophore-based virtual screening to molecular dynamics

The lack of effective treatment remains the biggest bottleneck in combating the current novel coronavirus (COVID-19) pandemic. Drug discovery is a complex and time-consuming process, while various in silico methods dramatically reduce the time and cost of this process. The infection begins with the binding of the receptor-binding domain (RBD) of Spike (S) glycoprotein from SARS-CoV-2 to the host angiotensin-converting enzyme (ACE2) receptor. We, therefore, present computational screening methods aimed to identify inhibitors potentially able to target RBD. For this purpose, pharmacophore mapping, molecular docking, and molecular dynamics (MD) simulations were performed to screen potential candidates against ACE2/SARS-CoV-2. In particular, pharmacophore-based virtual screening used over a hundred million compounds to construct protein-protein interactions (PPIs) inhibitor library. In conclusion, PubChem-84280085 compound is suggested as a potential PPIs inhibitor for preventing SARS-CoV-2 RBD/ACE2 interactions.