TY - JOUR
T1 - Mizoribine inhibits hepatitis C virus RNA replication
T2 - Effect of combination with interferon-α
AU - Naka, Kazuhito
AU - Ikeda, Masanori
AU - Abe, Ken Ichi
AU - Dansako, Hiromichi
AU - Kato, Nobuyuki
N1 - Funding Information:
We thank T. Nakamura, A. Morishita, and T. Maeta for their helpful experimental assistance. This work was supported by Grants-in-Aid for the third-term comprehensive 10-year strategy for cancer control, and for research on hepatitis from the Ministry of Health, Labor, and Welfare of Japan, and by Grants-in-Aid for scientific research from the Organization for Pharmaceutical Safety and Research (OPSR).
PY - 2005/5/13
Y1 - 2005/5/13
N2 - Interferon (IFN)-α monotherapy, as well as the more effective combination therapy of IFN-α and ribavirin, are currently used for patients with chronic hepatitis C caused by hepatitis C virus (HCV) infection, although the mechanisms of the antiviral effects of these reagents on HCV remain ambiguous, and side effects such as anemia due to the administration of ribavirin present a problem for patients who are advanced in years. Using a recently developed reporter assay system in which genome-length dicistronic HCV RNA encoding Renilla luciferase gene was found to replicate efficiently, we found that mizoribine, an imidazole nucleoside, inhibited HCV RNA replication. The anti-HCV activity of mizoribine (IC50: approximately 100 μM) was similar to that of ribavirin. Using this genome-length HCV RNA replication monitor system, we were the first to demonstrate that the combination of IFN-α and ribavirin exhibited more effective anti-HCV activity than the use of IFN-α alone. Moreover, we found that the anti-HCV activity of mizoribine in co-treatment with IFN-α was at least equivalent to that of ribavirin. This effect was apparent in the presence of at least 5 μM mizoribine. Since mizoribine is currently used in several clinical applications and has not been associated with severe side effects, mizoribine is considered to be of potential use as a new anti-HCV reagent in combination with IFN-α.
AB - Interferon (IFN)-α monotherapy, as well as the more effective combination therapy of IFN-α and ribavirin, are currently used for patients with chronic hepatitis C caused by hepatitis C virus (HCV) infection, although the mechanisms of the antiviral effects of these reagents on HCV remain ambiguous, and side effects such as anemia due to the administration of ribavirin present a problem for patients who are advanced in years. Using a recently developed reporter assay system in which genome-length dicistronic HCV RNA encoding Renilla luciferase gene was found to replicate efficiently, we found that mizoribine, an imidazole nucleoside, inhibited HCV RNA replication. The anti-HCV activity of mizoribine (IC50: approximately 100 μM) was similar to that of ribavirin. Using this genome-length HCV RNA replication monitor system, we were the first to demonstrate that the combination of IFN-α and ribavirin exhibited more effective anti-HCV activity than the use of IFN-α alone. Moreover, we found that the anti-HCV activity of mizoribine in co-treatment with IFN-α was at least equivalent to that of ribavirin. This effect was apparent in the presence of at least 5 μM mizoribine. Since mizoribine is currently used in several clinical applications and has not been associated with severe side effects, mizoribine is considered to be of potential use as a new anti-HCV reagent in combination with IFN-α.
KW - HCV RNA replication system
KW - Hepatitis C virus
KW - HuH-7
KW - Interferon
KW - Mizoribine
KW - Ribavirin
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U2 - 10.1016/j.bbrc.2005.03.062
DO - 10.1016/j.bbrc.2005.03.062
M3 - Article
C2 - 15809077
AN - SCOPUS:16244415552
SN - 0006-291X
VL - 330
SP - 871
EP - 879
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
