The SARS-CoV-2 main protease (M-pro) is a crucial enzymefor viral replication and has been considered an attractive drug targetfor the treatment of COVID-19. In this study, virtual screening techniquesand in vitro assays were combined to identify novelM(pro) inhibitors starting from around 8000 FDA-approveddrugs. the docking analysis highlighted 17 promising best hits, biologically characterized in terms of their M-pro inhibitory activity. among them, 7 cephalosporins and theoral anticoagulant betrixaban were able to block the enzyme activityin the micromolar range with no cytotoxic effect at the highest concentrationtested. after the evaluation of the degree of conservation of M-pro 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 associatedto its antithrombotic effect could pave the way for its possible usein the treatment of hospitalized COVID-19 patients.
Ambrosio, F.a., Costa, G., Romeo, I., Esposito, F., Alkhatib, M., Salpini, R., et al. (2023). Targeting SARS-CoV-2 Main Protease: A Successful Story Guided by an In Silico Drug Repurposing Approach. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 63(11) [10.1021/acs.jcim.3c00282].
Targeting SARS-CoV-2 Main Protease: A Successful Story Guided by an In Silico Drug Repurposing Approach
Alkhatib, Mohammad;Salpini, Romina;Svicher, Valentina;Ceccherini-Silberstein, Francesca;Artese, Anna
2023-06-12
Abstract
The SARS-CoV-2 main protease (M-pro) is a crucial enzymefor viral replication and has been considered an attractive drug targetfor the treatment of COVID-19. In this study, virtual screening techniquesand in vitro assays were combined to identify novelM(pro) inhibitors starting from around 8000 FDA-approveddrugs. the docking analysis highlighted 17 promising best hits, biologically characterized in terms of their M-pro inhibitory activity. among them, 7 cephalosporins and theoral anticoagulant betrixaban were able to block the enzyme activityin the micromolar range with no cytotoxic effect at the highest concentrationtested. after the evaluation of the degree of conservation of M-pro 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 associatedto its antithrombotic effect could pave the way for its possible usein the treatment of hospitalized COVID-19 patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
