Why All the Fury over Furin?
J Med Chem
; 65(4): 2747-2784, 2022 02 24.
Artigo
em Inglês
| 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:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Peptídeos
/
Furina
/
Bibliotecas de Moléculas Pequenas
/
Glicoproteína da Espícula de Coronavírus
/
SARS-CoV-2
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
J Med Chem
Assunto da revista:
Química
Ano de publicação:
2022
Tipo de documento:
Artigo
País de afiliação:
Acs.jmedchem.1c00518
Similares
MEDLINE
...
LILACS
LIS