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Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811.

Abstract：

:Hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma. We recently discovered that the immunosuppressant cyclosporin A (CsA) and its analogue lacking immunosuppressive function, NIM811, strongly suppress the replication of HCV in cell culture. Inhibition of a cellular replication cofactor, cyclophilin (CyP) B, is critical for its anti-HCV effects. Here, we explored the potential use of CyP inhibitors for HCV treatment by analyzing the HCV replicon system. Treatment with CsA and NIM811 for 7 days reduced HCV RNA levels by 2-3 logs, and treatment for 3 weeks reduced HCV RNA to undetectable levels. NIM811 exerted higher anti-HCV activity than CsA at lower concentrations. Both CyP inhibitors rapidly reduced HCV RNA levels even further in combination with IFNalpha without modifying the IFNalpha signal transduction pathway. In conclusion, CyP inhibitors may provide a novel strategy for anti-HCV treatment.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Goto K,Watashi K,Murata T,Hishiki T,Hijikata M,Shimotohno K

doi

10.1016/j.bbrc.2006.03.059

subject

Has Abstract

pub_date

2006-05-12 00:00:00

pages

879-84

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)00590-0

journal_volume

343

pub_type

杂志文章

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