The infection of host cells by COVID-19 mediated by the binding of its RBD from SARS-CoV-2 to the ACE2 receptor.
•
Rational drug design applied on over 100 million compounds to discover potential inhibitor against SARS-CoV-2 Spike RBD.
•
PubChem 84,280,085 compound is suggested as a potential PPIs inhibitor to demolish SARS-CoV-2 RBD/ACE2 interactions.
Abstract
The lack of effective treatment remains a bottleneck in combating the current coronavirus family pandemic, particularly coronavirus 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection of host cells by SARS-CoV-2 is mediated by the binding of its receptor-binding domain (RBD) on the spike (S) glycoprotein to the host angiotensin-converting enzyme (ACE2) receptor. As all developed and available vaccines against COVID-19 do not provide long-term immunity, the creation of an effective drug for the treatment of COVID-19 is necessary and cannot be ignored. Therefore, the aim of this study is to present a computational screening method to identify potential inhibitor candidates with a high probability of blocking the binding of RBD to the ACE2 receptor. Pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations, and binding free-energy analyses were performed to identify potential inhibitor candidates against ACE2/SARS-CoV-2. In conclusion, we propose the compound PubChem-84280085 as a potential inhibitor of protein–protein interactions to disrupt the binding of the SARS-CoV-2-RBD to the ACE2 receptor.
Graphical abstract
Keywords
SARS-CoV-2
Drug design
Pharmacophore
Virtual screening
Molecular docking
Molecular dynamics
Protein–protein interaction
Data availability
No data was used for the research described in the article.