Screening of Mpro Protease (SARS-CoV-2) Covalent Inhibitors from an Anthocyanin-Rich Blueberry Extract Using an HRMS-Based Analytical Platform.
Molecules
; 29(11)2024 Jun 06.
Article
en En
| MEDLINE
| ID: mdl-38893578
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Inhibidores de Proteasas
/
Extractos Vegetales
/
Arándanos Azules (Planta)
/
Proteasas 3C de Coronavirus
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SARS-CoV-2
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Antocianinas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Suiza