Research Repository

Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein.

Deganutti, Giuseppe and Prischi, Filippo and Reynolds, Christopher A (2021) 'Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein.' Journal of Computer-Aided Molecular Design, 35 (2). 195 - 207. ISSN 0920-654X

Binder3 (1).pdf - Accepted Version

Download (7MB) | Preview


The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The first interaction between the virus and the host cell is mediated by the spike protein on the virus surface and the human angiotensin-converting enzyme (ACE2). Small molecules able to bind the receptor-binding domain (RBD) of the spike protein and disrupt the binding to ACE2 would offer an important tool for slowing, or even preventing, the infection. Here, we screened 2421 approved small molecules in silico and validated the docking outcomes through extensive molecular dynamics simulations. Out of six drugs characterized as putative RBD binders, the cephalosporin antibiotic cefsulodin was further assessed for its effect on the binding between the RBD and ACE2, suggesting that it is important to consider the dynamic formation of the heterodimer between RBD and ACE2 when judging any potential candidate.

Item Type: Article
Uncontrolled Keywords: Cefsulodin, Antiviral Agents, Drug Evaluation, Preclinical, Binding Sites, Computer Simulation, Small Molecule Libraries, Molecular Dynamics Simulation, Molecular Docking Simulation, Spike Glycoprotein, Coronavirus, Angiotensin-Converting Enzyme 2
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 29 Mar 2021 12:41
Last Modified: 23 Nov 2021 16:10

Actions (login required)

View Item View Item