Why All the Fury over Furin?
J Med Chem
; 65(4): 2747-2784, 2022 02 24.
Artículo
en Inglés
| MEDLINE | ID: covidwho-2275124
ABSTRACT
Analysis of the SARS-CoV-2 sequence revealed a multibasic furin cleavage site at the S1/S2 boundary of the spike protein distinguishing this virus from SARS-CoV. Furin, the best-characterized member of the mammalian proprotein convertases, is an ubiquitously expressed single pass type 1 transmembrane protein. Cleavage of SARS-CoV-2 spike protein by furin promotes viral entry into lung cells. While furin knockout is embryonically lethal, its knockout in differentiated somatic cells is not, thus furin provides an exciting therapeutic target for viral pathogens including SARS-CoV-2 and bacterial infections. Several peptide-based and small-molecule inhibitors of furin have been recently reported, and select cocrystal structures have been solved, paving the way for further optimization and selection of clinical candidates. This perspective highlights furin structure, substrates, recent inhibitors, and crystal structures with emphasis on furin's role in SARS-CoV-2 infection, where the current data strongly suggest its inhibition as a promising therapeutic intervention for SARS-CoV-2.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Péptidos
/
Furina
/
Bibliotecas de Moléculas Pequeñas
/
Glicoproteína de la Espiga del Coronavirus
/
SARS-CoV-2
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
J Med Chem
Asunto de la revista:
Química
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
Acs.jmedchem.1c00518
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