A hybrid structure determination approach to investigate the druggability of the nucleocapsid protein of SARS-CoV-2.
Nucleic Acids Res
; 51(9): 4555-4571, 2023 05 22.
Artículo
en Inglés
| MEDLINE | ID: covidwho-2275338
ABSTRACT
The pandemic caused by SARS-CoV-2 has called for concerted efforts to generate new insights into the biology of betacoronaviruses to inform drug screening and development. Here, we establish a workflow to determine the RNA recognition and druggability of the nucleocapsid N-protein of SARS-CoV-2, a highly abundant protein crucial for the viral life cycle. We use a synergistic method that combines NMR spectroscopy and protein-RNA cross-linking coupled to mass spectrometry to quickly determine the RNA binding of two RNA recognition domains of the N-protein. Finally, we explore the druggability of these domains by performing an NMR fragment screening. This workflow identified small molecule chemotypes that bind to RNA binding interfaces and that have promising properties for further fragment expansion and drug development.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Desarrollo de Medicamentos
/
Proteínas de la Nucleocápside de Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Tratamiento Farmacológico de COVID-19
Tipo de estudio:
Estudio pronóstico
/
Ensayo controlado aleatorizado
Límite:
Humanos
Idioma:
Inglés
Revista:
Nucleic Acids Res
Año:
2023
Tipo del documento:
Artículo
País de afiliación:
Nar
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