Screening of Mpro Protease (SARS-CoV-2) Covalent Inhibitors from an Anthocyanin-Rich Blueberry Extract Using an HRMS-Based Analytical Platform

Autor: Alessandra Altomare, Giovanna Baron, Giulia Cambiaghi, Giulio Ferrario, Beatrice Zoanni, Larissa Della Vedova, Giulio Maria Fumagalli, Sarah D’Alessandro, Silvia Parapini, Serena Vittorio, Giulio Vistoli, Patrizia Riso, Marina Carini, Serena Delbue, Giancarlo Aldini
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecules, Vol 29, Iss 11, p 2702 (2024)
Druh dokumentu: article
ISSN: 29112702
1420-3049
DOI: 10.3390/molecules29112702
Popis: Background: The viral main protease (Mpro) of SARS-CoV-2 has been recently proposed as a key target to inhibit virus replication in the host. Therefore, molecules that can bind the catalytic site of Mpro could be considered as potential drug candidates in the treatment of SARS-CoV-2 infections. Here we proposed the application of a state-of-the-art analytical platform which combines metabolomics and protein structure analysis to fish-out potential active compounds deriving from a natural matrix, i.e., a blueberry extract. Methods: The experiments focus on finding MS covalent inhibitors of Mpro that contain in their structure a catechol/pyrogallol moiety capable of binding to the nucleophilic amino acids of the enzyme’s catalytic site. Results: Among the potential candidates identified, the delphinidin-3-glucoside showed the most promising results. Its antiviral activity has been confirmed in vitro on Vero E6 cells infected with SARS-CoV-2, showing a dose-dependent inhibitory effect almost comparable to the known Mpro inhibitor baicalin. The interaction of delphinidin-3-glucoside with the Mpro pocket observed was also evaluated by computational studies. Conclusions: The HRMS analytical platform described proved to be effective in identifying compounds that covalently bind Mpro and are active in the inhibition of SARS-CoV-2 replication, such as delphinidin-3-glucoside.
Databáze: Directory of Open Access Journals
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