Multiple cyclophilins involved in different cellular pathways mediate HCV replication.
Virology
; 397(1): 43-55, 2010 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-19932913
ABSTRACT
Three cyclophilin inhibitors (DEBIO-025, SCY635, and NIM811) are currently in clinical trials for hepatitis C therapy. The mechanism of action of these, however, is not completely understood. There are at least 16 cyclophilins expressed in human cells which are involved in a diverse set of cellular processes. Large-scale siRNA experiments, chemoproteomic assays with cyclophilin binding compounds, and mRNA profiling of HCV replicon containing cells were used to identify the cyclophilins that are instrumental to HCV replication. The previously reported cyclophilin A was confirmed and additional cyclophilin containing pathways were identified. Together, the experiments provide strong evidence that NIM811 reduces viral replication by inhibition of multiple cyclophilins and pathways with protein trafficking as the most strongly and persistently affected pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
/
Hepacivirus
/
Ciclofilinas
/
Interações Hospedeiro-Patógeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article