Identification, design and synthesis of novel pyrazolopyridine influenza virus nonstructural protein 1 antagonists.
Bioorg Med Chem Lett
; 29(9): 1113-1119, 2019 05 01.
Article
en En
| MEDLINE
| ID: mdl-30852083
ABSTRACT
Nonstructural protein 1 (NS1) plays a crucial function in the replication, spread, and pathogenesis of influenza virus by inhibiting the host innate immune response. Here we report the discovery and optimization of novel pyrazolopyridine NS1 antagonists that can potently inhibit influenza A/PR/8/34 replication in MDCK cells, rescue MDCK cells from cytopathic effects of seasonal influenza A strains, reverse NS1-dependent inhibition of IFN-ß gene expression, and suppress the slow growth phenotype in NS1-expressing yeast. These pyrazolopyridines will enable researchers to investigate NS1 function during infection and how antagonists can be utilized in the next generation of treatments for influenza infection.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Virus de la Influenza A
/
Pirazoles
/
Piridinas
/
Diseño de Fármacos
/
Proteínas no Estructurales Virales
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article