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

Kaku Goto, Koichi Watashi, Takayuki Murata, Takayuki Hishiki, Makoto Hijikata, Kunitada Shimotohno

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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 IFNα without modifying the IFNα signal transduction pathway. In conclusion, CyP inhibitors may provide a novel strategy for anti-HCV treatment.

Original languageEnglish
Pages (from-to)879-884
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume343
Issue number3
DOIs
Publication statusPublished - 12-05-2006

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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