Profiling of coronaviral Mpro and enteroviral 3Cpro specificity provides a framework for the development of broad-spectrum antiviral compounds.
Protein Sci
; 33(9): e5139, 2024 Sep.
Article
de En
| MEDLINE
| ID: mdl-39150063
ABSTRACT
The main protease from coronaviruses and the 3C protease from enteroviruses play a crucial role in processing viral polyproteins, making them attractive targets for the development of antiviral agents. In this study, we employed a combinatorial chemistry approach-HyCoSuL-to compare the substrate specificity profiles of the main and 3C proteases from alphacoronaviruses, betacoronaviruses, and enteroviruses. The obtained data demonstrate that coronavirus Mpros exhibit overlapping substrate specificity in all binding pockets, whereas the 3Cpro from enterovirus displays slightly different preferences toward natural and unnatural amino acids at the P4-P2 positions. However, chemical tools such as substrates, inhibitors, and activity-based probes developed for SARS-CoV-2 Mpro can be successfully applied to investigate the activity of the Mpro from other coronaviruses as well as the 3Cpro from enteroviruses. Our study provides a structural framework for the development of broad-spectrum antiviral compounds.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Antiviraux
/
Enterovirus
/
Protéases 3C des coronavirus
/
SARS-CoV-2
Limites:
Humans
Langue:
En
Journal:
Protein Sci
/
Protein sci
/
Protein science
Sujet du journal:
BIOQUIMICA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Pologne
Pays de publication:
États-Unis d'Amérique