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

Autor: Altomare A; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Baron G; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Cambiaghi G; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Ferrario G; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Zoanni B; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Della Vedova L; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Fumagalli GM; Unitech OMICs, Università degli Studi di Milano, Viale Ortles 22/4, 20139 Milan, Italy., D'Alessandro S; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Carlo Pascal 36, 20133 Milan, Italy., Parapini S; Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Carlo Pascal 36, 20133 Milan, Italy., Vittorio S; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Vistoli G; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Riso P; Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Via Luigi Mangiagalli 25, 20133 Milan, Italy., Carini M; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy., Delbue S; Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Carlo Pascal 36, 20133 Milan, Italy., Aldini G; Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2024 Jun 06; Vol. 29 (11). Date of Electronic Publication: 2024 Jun 06.
DOI: 10.3390/molecules29112702
Abstrakt: Background: The viral main protease (M pro ) 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 M pro 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 M pro 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 M pro inhibitor baicalin. The interaction of delphinidin-3-glucoside with the M pro pocket observed was also evaluated by computational studies.
Conclusions: The HRMS analytical platform described proved to be effective in identifying compounds that covalently bind M pro and are active in the inhibition of SARS-CoV-2 replication, such as delphinidin-3-glucoside.
Databáze: MEDLINE
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