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Investigation of the host factors associated with influenza virus replication based on the cyclosporine derivatives

Research Project

Project/Area Number 19K08962
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionTokai University (2020-2022)
Juntendo University (2019)

Principal Investigator

Yamamoto Norio  東海大学, 医学部, 教授 (40323703)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsインフルエンザウイルス / シクロスポリン / インフルエンザ / 宿主因子
Outline of Research at the Start

これまでに申請者はシクロスポリン(CsA)に抗インフルエンザウイルス活性があることを見出したが、そのメカニズムはまだ明らかになっていない。そこで本研究では、CsAによるインフルエンザウイルス増殖抑制機構を解明するため、独自に構築したCsA固定化ビーズを用いて新規CsA結合タンパク質の探索と、その機能の解析を行う。

Outline of Final Research Achievements

We identified cyclosporin A (CsA) and its derivatives as the candidates of the anti-influenza virus drugs with novel molecular targets. The infection experiments using siRNAs revealed that the known molecular targets of CsA were not involved in the viral replication process. Therefore, we purified and analyzed CsA-binding proteins by the chemical pull-down method using CsA-immobilized beads. As a result, some CsA-binding proteins were identified by MS analysis. Analysis using cells in which the identified genes were knocked out allowed us to narrow down candidate host factors associated with viral propagation.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、新たな機序による抗インフルエンザウイルス薬の出発点としてCsAが同定された。また、ウイルスの増殖に関与する新たな細胞側の因子の候補を同定することができた。本研究の成果は、薬剤耐性ウイルスに対応可能な新しい抗インフルエンザウイルス薬の開発につながる可能性があり、大きな社会的意義がある。また、新たな宿主因子の発見からウイルスタンパク質や細胞側タンパク質の新たな機能が明らかになることが期待され、学術的にも大きな意義があると思われる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (19 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (5 results) (of which Invited: 2 results) Book (1 results)

  • [Int'l Joint Research] National Institute of Chemistry/University of Ljubljana(スロベニア)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] SARS-CoV-2 evolution among patients with immunosuppression in a nosocomial cluster of a Japanese medical center during the Delta (AY.29 sublineage) surge2023

    • Author(s)
      Hosaka Yoshie、Yan Yan、Naito Toshio、Oyama Rieko、Tsuchiya Koji、Yamamoto Norio、Nojiri Shuko、Hori Satoshi、Takahashi Kazuhiko、Tabe Yoko
    • Journal Title

      Frontiers in Microbiology

      Volume: 14 Pages: 1-4

    • DOI

      10.3389/fmicb.2023.944369

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suitability of NIID‐MDCK cells as a substrate for cell‐based influenza vaccine development from the perspective of adventitious virus susceptibility2022

    • Author(s)
      Hamamoto Itsuki、Takahashi Hitoshi、Shimasaki Noriko、Nakamura Kazuya、Mizuta Katsumi、Sato Ko、Nishimura Hidekazu、Yamamoto Norio、Hasegawa Hideki、Odagiri Takato、Tashiro Masato、Nobusawa Eri
    • Journal Title

      Microbiology and Immunology

      Volume: 66 Issue: 7 Pages: 361-370

    • DOI

      10.1111/1348-0421.12985

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, Synthesis and Evaluation of Fused Bicyclo[2.2.2]octene as a Potential Core Scaffold for the Non-Covalent Inhibitors of SARS-CoV-2 3CLpro Main Protease2022

    • Author(s)
      Herlah Barbara、Hoivik Andrej、Jamsek Luka、Valjavec Katja、Yamamoto Norio、Hoshino Tyuji、Kranjc Kristof、Perdih Andrej
    • Journal Title

      Pharmaceuticals

      Volume: 15 Issue: 5 Pages: 539-539

    • DOI

      10.3390/ph15050539

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular characterization of SARS-CoV-2 detected in Tokyo, Japan during five waves: Identification of the amino acid substitutions associated with transmissibility and severity2022

    • Author(s)
      Tsuchiya Koji、Yamamoto Norio、Hosaka Yoshie、Wakita Mitsuru、Hiki Makoto、Matsushita Yasushi、Mori Hirotake、Hori Satoshi、Misawa Shigeki、Miida Takashi、Nojiri Shuko、Takahashi Kazuhisa、Naito Toshio、Tabe Yoko
    • Journal Title

      Frontiers in Microbiology

      Volume: 13 Pages: 1-4

    • DOI

      10.3389/fmicb.2022.912061

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunological imprint on peripheral blood in kidney transplant recipients after two doses of SARS-CoV-2 mRNA vaccination in Japan2022

    • Author(s)
      Takiguchi Shinya、Tomita Yusuke、Uehara Saeko、Tateishi Koichiro、Yamamoto Norio、Nakamura Michio
    • Journal Title

      Frontiers in Medicine

      Volume: 9 Pages: 1-4

    • DOI

      10.3389/fmed.2022.999374

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of Serial Passage on the Pathogenicity and Immunogenicity of Vaccinia Virus LC16m8 Strain2021

    • Author(s)
      Eto Akiko、Yamamoto Norio、Kanatani Yasuhiro
    • Journal Title

      Biology

      Volume: 10 Issue: 11 Pages: 1158-1158

    • DOI

      10.3390/biology10111158

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA Sequencing Identifies a Common Physiology in Vancomycin- and Ciprofloxacin-Tolerant Staphylococcus aureus Induced by ileS Mutations2020

    • Author(s)
      Singh M, Matsuo M, Sasaki T, Hishinuma T, Yamamoto N, Morimoto Y, Kirikae T, Hiramatsu K
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 64 Issue: 10 Pages: 1-6

    • DOI

      10.1128/aac.00827-20

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection of <i>Arcobacter</i> Species in Human Stool Samples by Culture and Real-time PCR2020

    • Author(s)
      Yamauchi Y, Uehara Y, Boutin S, Yamamoto N, Kuwahara-Arai K, Kirikae T, Hiramatsu K, Zimmermann S
    • Journal Title

      Juntendo Medical Journal

      Volume: 66 Issue: 5 Pages: 431-438

    • DOI

      10.14789/jmj.2020.66.JMJ19-OA05

    • NAID

      130007933296

    • ISSN
      2187-9737, 2188-2126
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro2020

    • Author(s)
      Yamamoto N, Matsuyama S, Hoshino T, and Yamamoto N
    • Journal Title

      bioRxiv

      Volume: 1 Pages: 1-9

    • DOI

      10.1101/2020.04.06.026476

    • Related Report
      2020 Research-status Report
  • [Journal Article] Comparison of suspension MDCK cells, adherent MDCK cells, and LLC‐MK2 cells for selective isolation of influenza viruses to be used as vaccine seeds2019

    • Author(s)
      Harada Yuichi、Takahashi Hitoshi、Trusheim Heidi、Roth Bernhard、Mizuta Katsumi、Hirata‐Saito Asumi、Ogane Teruko、Odagiri Takato、Tashiro Masato、Yamamoto Norio
    • Journal Title

      Influenza and Other Respiratory Viruses

      Volume: 14 Issue: 2 Pages: 204-209

    • DOI

      10.1111/irv.12694

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systematic evaluation of suspension MDCK cells, adherent MDCK cells, and LLC-MK2 cells for preparing influenza vaccine seed virus2019

    • Author(s)
      Nakamura Kazuya、Harada Yuichi、Takahashi Hitoshi、Trusheim Heidi、Bernhard Roth、Hamamoto Itsuki、Hirata-Saito Asumi、Ogane Teruko、Mizuta Katsumi、Konomi Nami、Konomi Yasushi、Asanuma Hideki、Odagiri Takato、Tashiro Masato、Yamamoto Norio
    • Journal Title

      Vaccine

      Volume: 37 Issue: 43 Pages: 6526-6534

    • DOI

      10.1016/j.vaccine.2019.08.064

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CpG ODN G9.1 as a novel nasal ODN adjuvant elicits complete protection from influenza virus infection without causing inflammatory immune responses2019

    • Author(s)
      Tateishi Koichiro、Fujihashi Kohtaro、Yamamoto Norio、Hasegawa Hideki、Ainai Akira、Sato Kayoko、Iho Sumiko、Yamamoto Saburo、Maeyama Jun-ichi、Odagiri Takato、Asanuma Hideki
    • Journal Title

      Vaccine

      Volume: 37 Issue: 36 Pages: 5382-5389

    • DOI

      10.1016/j.vaccine.2019.07.032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新型コロナウイルス感染症の予防・治療について2021

    • Author(s)
      山本典生
    • Organizer
      第 29 回日本臨床環境医学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 新型コロナウイルス研究の動向2020

    • Author(s)
      山本典生
    • Organizer
      東海大学2020年度研究交流会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 糖鎖に注目したCOVID-19重症化メカニズムの解析と重症化阻害薬の開発2020

    • Author(s)
      山本典生
    • Organizer
      東海大学2020年度研究交流会
    • Related Report
      2020 Research-status Report
  • [Presentation] 既承認薬からのSARS-CoV-2増殖阻害剤の効率的同定2020

    • Author(s)
      山本典生、平山令明
    • Organizer
      東海大学2020年度研究交流会
    • Related Report
      2020 Research-status Report
  • [Presentation] インフルエンザウイルス感染における細胞表層ヘパラン硫酸の関与2019

    • Author(s)
      御子神拓樹、臼井麻琴、阿部史弥、渡辺マコ、築地 信、山本典生、東 伸昭
    • Organizer
      第20回Pharmaco-Hematologyシンポジウム
    • Related Report
      2019 Research-status Report
  • [Book] 防災のサバイバル クイズでわかる生き残り大作戦!2021

    • Author(s)
      韓賢東、国崎信江、山本典生
    • Total Pages
      160
    • Publisher
      朝日新聞出版
    • ISBN
      9784023319455
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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