TY - JOUR
T1 - Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811
AU - Goto, Kaku
AU - Watashi, Koichi
AU - Murata, Takayuki
AU - Hishiki, Takayuki
AU - Hijikata, Makoto
AU - Shimotohno, Kunitada
N1 - Funding Information:
We thank Novartis (Basel, Swizerland) for providing the CsA derivative, NIM811. This work was supported by Grants-in-Aid for cancer research and for the second-term comprehensive 10-year strategies for cancer control from the Ministry of Health, Labor and Welfare. We were also supported by Grants-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology, by Grants-in-Aid for the Research for the Future program from the Japanese Society for the Promotion of Science, and by Grants-in-Aid for the Program for Promotion of Fundamental Studies in Health Science from the Organization for Pharmaceutical Safety.
PY - 2006/5/12
Y1 - 2006/5/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2006.03.059
DO - 10.1016/j.bbrc.2006.03.059
M3 - Article
C2 - 16564500
AN - SCOPUS:33645911783
SN - 0006-291X
VL - 343
SP - 879
EP - 884
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -