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ID 53955
フルテキストURL
著者
Ueda, Youki Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Takeda, Midori Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Mori, Kyoko Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Dansako, Hiromichi Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Wakita, Takaji Department of Virology II, National Institute of Infectious Disease
Kim, Hye-Sook Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University
Sato, Akira Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University
Wataya, Yusuke Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University
Ikeda, Masanori Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Kato, Nobuyuki Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
抄録
BACKGROUND: Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed.   METHODOLOGY/PRINCIPAL FINDINGS:     Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.    CONCLUSIONS/SIGNIFICANCE:    We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.
備考
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
発行日
2013-08-30
出版物タイトル
PLOS ONE
8巻
8号
出版者
PUBLIC LIBRARY SCIENCE
開始ページ
e72519
ISSN
1932-6203
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1371/journal.pone.0072519
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/53390
言語
English
著作権者
© 2013 Ueda et al.
論文のバージョン
publisher
査読
有り
DOI
PubMed ID
Web of Sience KeyUT