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Antiviral mechanism of new endoperoxide compounds showing antimalarial activity

Research Project

Project/Area Number 15K15142
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionOkayama University

Principal Investigator

Kato Nobuyuki  岡山大学, 医歯薬学総合研究科, 教授 (40150883)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsウイルス / 感染症 / 微生物 / 抗ウイルス剤 / 薬理作用機序 / 遺伝子解析 / マイクロアレイ解析
Outline of Final Research Achievements

We have carried out the study to clarify the anti-hepatitis C virus (HCV) mechanism of new anti-HCV compounds (N-89 and its derivative N-251). From N-89- or N-251-sensitive HCV-RNA-replicating cells (sensitive cells), we first established the cell lines possessing a N-89- or N-251-resistant phenotype (resistant cells). Using the sensitive and resistant cells, we analyzed the action mechanism of these compounds. The results appeared that both host and viral factors contribute to almost the same degree of the resistance to these compounds. Genetic analysis of HCVs derived from the resistant cells detected amino acids substitutions, which might be involved in the acquisition of resistance against these compounds. cDNA microarray analysis selected gene candidates, which might contribute to resistant acquisition. In addition, we demonstrated that these compounds showed antiviral effects against Japanese encephalitis virus, hepatitis B virus, and hepatitis E virus.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Evaluation of preclinical antimalarial drugs, which can overcome direct-acting antivirals-resistant hepatitis C viruses, using the viral reporter assay systems.2017

    • Author(s)
      Ueda Y, Dansako H, Sato S, Kim HS, Wataya Y, Doi H, Ikeda M, Kato N.
    • Journal Title

      Virus Res

      Volume: 235 Pages: 37-48

    • DOI

      10.1016/j.virusres.2017.03.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular mechanism underlying the suppression of CPB2 expression caused by persistent hepatitis C virus RNA replication.2016

    • Author(s)
      Sejima H, Satoh S, Dansako H, Honda M, Kaneko S, Ikeda M, Kato N.
    • Journal Title

      Acta Med Okayama

      Volume: 70 Pages: 75-88

    • NAID

      120005749825

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of resistance-associated NS5A mutations in hepatitis C virus on viral production and susceptibility to antiviral reagents.2016

    • Author(s)
      Nitta S, Asahina Y, Matsuda M, Yamada N, Sugiyama R, Masaki T, Suzuki R, Kato N, Watanabe M, Wakita T, Kato T.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34652-34652

    • DOI

      10.1038/srep34652

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Control of HCV Replication with iMIRs, a Novel Anti-RNAi Agent2015

    • Author(s)
      Saori Itami, Yutaka Eguchi, Takayuki Mizutani, Eriko Aoki, Tadaaki Ohgi, Masahiko Kuroda, Takahiro Ochiya, Nobuyuki Kato, Hiroshi I Suzuki, Norifumi Kawada and Yoshiki Murakami
    • Journal Title

      Molecular Therapy Nucleic Acids

      Volume: 4 Pages: e219-e219

    • DOI

      10.1038/mtna.2014.71

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of FKBP6 in hepatitis C virus replication2015

    • Author(s)
      Kasai H, Kawakami Y, Yokoe H, Yoshimura K, Matsuda M, Yasumoto J, Maekawa S, Yamashita A, Tanaka T, Ikeda M, Kato N, Okamoto T, Matsuura Y, Sakamoto N, Enomoto N, Takeda S, Fujii H, Tsubuki M, Kusunoki M, Moriishi K.
    • Journal Title

      Scientific reports

      Volume: 5 Issue: 1 Pages: 16699-16699

    • DOI

      10.1038/srep16699

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Both host and viral factors contribute to the resistance to preclinical anti-HCV drugs, N-89 and N-251.2016

    • Author(s)
      Gu W, Ueda Y, Dansako H, Satoh S, Kato N.
    • Organizer
      The 64th Annual Meeting of The Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Genetic characterization of HCVs obtained from HCV-RNA-replicating cells possessing a DAA-, N-89-, or N-251-resistant phenotype.2016

    • Author(s)
      Ueda Y, Dansako H, Satoh S, Ikeda M, Kato N.
    • Organizer
      The 64th Annual Meeting of The Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] DAA製剤によるHCV治療におけるN-89/N-251の有用性とそれらの作用機序の解析2016

    • Author(s)
      上田 優輝、團迫 浩方、佐藤 伸哉、池田 正徳、加藤 宣之
    • Organizer
      第26回抗ウイルス療法学会総会
    • Place of Presentation
      名古屋市立大学、名古屋
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Antimalarial preclinical drugs, N-89 and N-251, overcome various DAAs-resistant HCVs.2015

    • Author(s)
      Youki Ueda, Hiromichi Dansako, Shinya Satoh, Hye-Sook Kim, Hiroyuki Doi, Yusuke Wataya, Masanori Ikeda, Nobuyuki Kato.
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議場、福岡
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Antimalarial preclinical drugs, N-89 and N-251, overcome various DAAs-resistant HCVs.2015

    • Author(s)
      Youki Ueda, Hiromichi Dansako, Shinya Satoh, Hye-Sook Kim, Hiroyuki Doi, Yusuke Wataya, Masanori Ikeda, Nobuyuki Kato.
    • Organizer
      22nd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Strasbourg, France
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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