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An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors

Trezza, Alfonso and Iovinelli, Daniele and Santucci, Annalisa and Prischi, Filippo and Spiga, Ottavia (2020) 'An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors.' Scientific Reports, 10 (1). 13866-. ISSN 2045-2322

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The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein – ACE2 interaction inhibitor. Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction.

Item Type: Article
Uncontrolled Keywords: Humans; Pneumonia, Viral; Coronavirus Infections; Aminopyridines; Peptidyl-Dipeptidase A; Computational Biology; Binding Sites; Protein Conformation; Protein Binding; Benzodioxoles; Drug Discovery; Molecular Dynamics Simulation; Drug Repositioning; Pandemics; Protein Interaction Maps; Molecular Docking Simulation; Spike Glycoprotein, Coronavirus; Simeprevir; Protein Domains; Betacoronavirus; COVID-19; Angiotensin-Converting Enzyme 2; SARS-CoV-2
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 17 Aug 2020 13:42
Last Modified: 18 Aug 2022 12:25

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