University of Cagliari
open
Targeting SARS-CoV-2 Main Protease: A Successful Story Guided by an In Silico Drug Repurposing Approach
Francesca Esposito;Angela Corona;Paolo Malune;Enzo Tramontano;
2023-01-01
Abstract
The SARS-CoV-2 main protease (Mpro) is a crucial enzyme for viral replication and has been considered an attractive drug target for the treatment of COVID-19. In this study, virtual screening techniques and in vitro assays were combined to identify novel Mpro inhibitors starting from around 8000 FDA-approved drugs. The docking analysis highlighted 17 promising best hits, biologically characterized in terms of their Mpro inhibitory activity. Among them, 7 cephalosporins and the oral anticoagulant betrixaban were able to block the enzyme activity in the micromolar range with no cytotoxic effect at the highest concentration tested. After the evaluation of the degree of conservation of Mpro residues involved in the binding with the studied ligands, the ligands’ activity on SARS-CoV-2 replication was assessed. The ability of betrixaban to affect SARS-CoV-2 replication associated to its antithrombotic effect could pave the way for its possible use in the treatment of hospitalized COVID-19 patients
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| Ambrosio et al ACS JCIM 2023.pdf open access
Type: versione post-print
Size 7.82 MB
Format Adobe PDF
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7.82 MB | Adobe PDF | View/Open |
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