Leveraging SARS-CoV-2 Main Protease (Mpro) for COVID-19 Mitigation with Selenium-Based Inhibitors
Viviana De Luca, Andrea Angeli, Alessio Nocentini, Paola Gratteri, Silvia Pratesi, Damiano Tanini, Vincenzo Carginale, Antonella Capperucci, Claudiu T Supuran, Clemente Capasso
International Journal of Molecular Sciences, doi:10.3390/ijms25020971
The implementation of innovative approaches is crucial in an ongoing endeavor to mitigate the impact of COVID-19 pandemic. The present study examines the strategic application of the SARS-CoV-2 Main Protease (M pro ) as a prospective instrument in the repertoire to combat the virus. The cloning, expression, and purification of M pro , which plays a critical role in the viral life cycle, through heterologous expression in Escherichia coli in a completely soluble form produced an active enzyme. The hydrolysis of a specific substrate peptide comprising a six-amino-acid sequence (TSAVLQ) linked to a p-nitroaniline (pNA) fragment together with the use of a fluorogenic substrate allowed us to determine effective inhibitors incorporating selenium moieties, such as benzoselenoates and carbamoselenoates. The new inhibitors revealed their potential to proficiently inhibit M pro with IC 50 -s in the low micromolar range. Our study contributes to the development of a new class of protease inhibitors targeting M pro , ultimately strengthening the antiviral arsenal against COVID-19 and possibly, related coronaviruses.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ijms25020971/s1.
Conflicts of Interest: The authors declare no conflicts of interest.
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