start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=8 article-no= start-page=e72519 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakedaMidori en-aut-sei=Takeda en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriKyoko en-aut-sei=Mori en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WakitaTakaji en-aut-sei=Wakita en-aut-mei=Takaji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoAkira en-aut-sei=Sato en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatayaYusuke en-aut-sei=Wataya en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatoNobuyuki en-aut-sei=Kato en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Virology II, National Institute of Infectious Disease affil-num=6 en-affil= kn-affil=Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University affil-num=7 en-affil= kn-affil=Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University affil-num=8 en-affil= kn-affil=Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University affil-num=9 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=10 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=1998 dt-pub=19980325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ヌクレオシド構造を基本骨格とする新規抗マラリア剤の開発およびその作用機序に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=金惠淑 kn-aut-sei=金 kn-aut-mei=惠淑 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=3 article-no= start-page=231 end-page=235 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20151201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=New antimalarial endoperoxides for drug-resistant Plasmodium falciparumn : The current situation kn-title=薬剤耐性マラリアに有望な新規抗マラリア薬開発の現況 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name=金惠淑 kn-aut-sei=金 kn-aut-mei=惠淑 aut-affil-num=1 ORCID= en-aut-name=KatamotoAkane en-aut-sei=Katamoto en-aut-mei=Akane kn-aut-name=片本茜 kn-aut-sei=片本 kn-aut-mei=茜 aut-affil-num=2 ORCID= en-aut-name=SatoAkira en-aut-sei=Sato en-aut-mei=Akira kn-aut-name=佐藤聡 kn-aut-sei=佐藤 kn-aut-mei=聡 aut-affil-num=3 ORCID= en-aut-name=WatayaYusuke en-aut-sei=Wataya en-aut-mei=Yusuke kn-aut-name=綿矢有佑 kn-aut-sei=綿矢 kn-aut-mei=有佑 aut-affil-num=4 ORCID= en-aut-name=DoiHiroyuki en-aut-sei=Doi en-aut-mei=Hiroyuki kn-aut-name=土居弘幸 kn-aut-sei=土居 kn-aut-mei=弘幸 aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=3 en-affil= kn-affil=東京理科大学薬学部 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 en-keyword=薬剤耐性マラリア kn-keyword=薬剤耐性マラリア en-keyword=ACT療法（artemisinin-based combination therapy） kn-keyword=ACT療法（artemisinin-based combination therapy） en-keyword=新薬開発 kn-keyword=新薬開発 en-keyword=環状過酸化物 kn-keyword=環状過酸化物 en-keyword=標的分子 kn-keyword=標的分子 END