Development of a new experimental NMR strategy for covalent cysteine protease inhibitors screening: toward enhanced drug discovery.
RSC Adv
; 14(37): 26829-26836, 2024 Aug 22.
Article
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| MEDLINE
| ID: mdl-39184001
ABSTRACT
In the development of antiviral drugs, proteases and polymerases are among the most important targets. Cysteine proteases, also known as thiol proteases, catalyze the degradation of proteins by cleaving peptide bonds using the nucleophilic thiol group of cysteine. As part of our research, we are examining how cysteine, an essential amino acid found in the active site of the main protease (Mpro) enzyme in SARS-CoV-2, interacts with electrophilic groups present in ethacrynic acid (EA) and compounds 4, 6, and 8 to form sulfur-carbon bonds. Nuclear magnetic resonance (NMR) spectroscopy was used to monitor the reaction rate between cysteine and Michael acceptors. We found that the inhibitory activity of these compounds towards Mpro is correlated to their chemical reactivity toward cysteine. This approach may serve as a valuable tool in drug development for detecting potential covalent inhibitors of Mpro and other cysteine proteases.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
RSC Adv
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido