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The development of the new therapeutic drug which based on the structure of the virus activation enzyme: The new control method of the highly pathogenic infectious diseases.

Research Project

Project/Area Number 15K09585
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionSagami Women's University

Principal Investigator

Okumura Yuushi  相模女子大学, 栄養科学部, 教授 (70294725)

Co-Investigator(Kenkyū-buntansha) 永野 ひかる  大阪府立大学, 公私立大学の部局等, 研究員 (10748924)
嶋田 昌子  相模女子大学, 栄養科学部, 教授 (30637369)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords高病原性ウイルス感染症 / ウイルス活性化酵素 / 膜結合型プロテアーゼ / 酵素阻害剤 / 高病原性感染症
Outline of Final Research Achievements

Cleavage of viral envelope glycoprotein, hemagglutinin (HA), by host cellular proteases is essential step for influenza virus to enter into the target cells. We identified that ubiquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, were candidates of HA-processing proteases of diverse highly pathogenic avian influenza (HPAI) viruses. In addition, we succeeded to reveal the crystal structure of MSPL/TMPRSS13. In this study, based on their structure, we first generated specific inhibitors for MSPL/TMPRSS13. To confirm the involvement of these proteases in HPAI virus infection, highly virulent virus (A/Crow/Kyoto/53/2004 (H5N1)) was infected into MSPL/TMPRSS13 stably expressed cells with or without their specific inhibitors. As a result, we concluded that these proteases specific inhibitors might be suppress HPAI virus multicycle replication and spreading. In vivo infectious experiments using their specific inhibitors are currently being investigated.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Reactive oxygen species up-regulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells.2018

    • Author(s)
      Yuushi Okumura et al.
    • Journal Title

      Am J Physiol Cell Physiol.

      Volume: 印刷中 Issue: 6 Pages: C721-C731

    • DOI

      10.1152/ajpcell.00184.2017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of cutaneous extracellular collagen contraction by phosphorylation status of p130Cas.2016

    • Author(s)
      Yuushi Okumura et al.
    • Journal Title

      J Physiol Sci.

      Volume: - Issue: 5 Pages: 613-622

    • DOI

      10.1007/s12576-016-0493-9

    • NAID

      40021302104

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural analysis of the TKB domain of ubiquitin ligase Cbl-b complexed with its small inhibitory peptide, Cblin2016

    • Author(s)
      Ohno A, Ochi A, Maita N, Ueji T, Bando A, Nakao R, Hirasaka K, Abe T, Teshima-Kondo S, Nemoto H, Okumura Y, Higashibata A, Yano S, Tochio H, Nikawa T
    • Journal Title

      Arch Biochem Biophys

      Volume: 594 Pages: 1-7

    • DOI

      10.1016/j.abb.2016.02.014

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] UCP3 is associated with Hax-1 in mitochondria in the presence of calcium ion2016

    • Author(s)
      Hirasaka K, Mills EM, Haruna M, Bando A, Ikeda C, Abe T, Kohno S, Nowinski SM, Lago CU, Akagi K, Tochio H, Ohno A, Teshima-Kondo S, Okumura Y, Nikawa T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 472 Issue: 1 Pages: 108-113

    • DOI

      10.1016/j.bbrc.2016.02.075

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Capric Acid Up-Regulates UCP3 Expression without PDK4 Induction in Mouse C2C12 Myotubes2016

    • Author(s)
      Abe T, Hirasaka K, Kohno S, Tomida C, Haruna M, Uchida T, Ohno A, Oarada M, Teshima-Kondo S, Okumura Y, Choi I, Aoyama T, Terao J, Nikawa T*.
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 62 Issue: 1 Pages: 32-39

    • DOI

      10.3177/jnsv.62.32

    • NAID

      130005148603

    • ISSN
      0301-4800, 1881-7742
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 無重力ストレスによる筋委縮における酸化ストレスの重要性2017

    • Author(s)
      奥村 裕司 他
    • Organizer
      日本病態プロテアーゼ学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 高病原性インフルエンザ感染に関わる宿主酵素MSPLと阻害ペプチドとの複合体構造2017

    • Author(s)
      奥村 裕司 他
    • Organizer
      日本栄養・食糧学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] II型膜貫通型セリンプロテアーゼMSPLとペプチド性阻害剤との複合体結晶構造解析2016

    • Author(s)
      奥村 裕司 他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨格筋細胞分化を制御する新たな機能性RNAの解明2016

    • Author(s)
      奥村 裕司 他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 廃用性筋委縮原因酵素Cbl-bと阻害ペプチドCblinとの複合体結晶構造解析2016

    • Author(s)
      奥村 裕司 他
    • Organizer
      日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2016-08-05
    • Related Report
      2016 Research-status Report
  • [Presentation] UCP3と Hax-1の相互作用様式の解明2015

    • Author(s)
      奥村 裕司 他
    • Organizer
      日本病態プロテアーゼ学会
    • Place of Presentation
      ANAクラウンプラザホテルグランコート名古屋
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
  • [Presentation] A novel myogenic functional residing in the 5'non-cording regain of Insulin receptor substrate-1(Irs-1) transcript2015

    • Author(s)
      Yuushi Okumura et al.
    • Organizer
      12th Asian Congress of Nutrition
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-05-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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