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Investigation for novel antiviral lead compounds focusing on the host adaptation mechanism of influenza virus

Research Project

Project/Area Number 18K15171
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49060:Virology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Arai Yasuha  京都府立医科大学, 医学(系)研究科(研究院), 研究員 (80793182)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsインフルエンザウイルス / 宿主因子 / ヒト適応性 / ウイルス複製 / ウイルス学 / 抗ウイルス薬
Outline of Final Research Achievements

We have identified novel adaptive mutations in humans by comprehensively searching for adaptive mutations acquired by avian influenza virus in infected patients. The purpose of this study was to identify host factors essential for viral replication using the mutant viruses as human adaptation model viruses.
We established an immunoprecipitation method that efficiently coprecipitates host factors that bind to polymerase complex, and selected multiple host factors that specifically bind to mutants by LC-MS / MS. We evaluated the effect of this factor on viral replication, but the factors that affect viral replication have not been identified. We are trying to select candidate factors more widely and create multiple knockdown cells.

Academic Significance and Societal Importance of the Research Achievements

ウイルス複製に重要な宿主因子を同定し、さらに宿主因子・ウイルス蛋白質の結合を阻害するリード化合物探索へ研究を展開する。現存の抗インフルエンザ薬は、特定のウイルス蛋白質の働きを抑えるが、ウイルス遺伝子の変異によって薬剤耐性ウイルスが出現する問題点がある。今後同定されるリード化合物は、ウイルス蛋白質に作用せずにその複製を阻害するため、既存の抗ウイルス薬の弱点を克服できる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (4 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] “Genetic tuning” of avian influenza virus host adaptation from birds to humans2020

    • Author(s)
      Arai Yasuha、Watanabe Yohei
    • Journal Title

      Biosafety and Health

      Volume: Online ahead of print Issue: 2 Pages: 1-3

    • DOI

      10.1016/j.bsheal.2020.11.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range2020

    • Author(s)
      Arai Yasuha、Kawashita Norihito、Elgendy Emad Mohamed、Ibrahim Madiha Salah、Daidoji Tomo、Ono Takao、Takagi Tatsuya、Nakaya Takaaki、Matsumoto Kazuhiko、Watanabe Yohei
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 1

    • DOI

      10.1128/jvi.01582-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity2020

    • Author(s)
      Arai Yasuha、Elgendy Emad Mohamed、Daidoji Tomo、Ibrahim Madiha Salah、Ono Takao、Sriwilaijaroen Nongluk、Suzuki Yasuo、Nakaya Takaaki、Matsumoto Kazuhiko、Watanabe Yohei
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 18

    • DOI

      10.1128/jvi.01210-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PB2 mutations arising during H9N2 influenza evolution in the Middle East confer enhanced replication and growth in mammals.2019

    • Author(s)
      Arai Y, Kawashita N, Ibrahim MS, Elgendy EM, Daidoji T, Ono T, Takagi T, Nakaya T, Matsumoto K, Watanabe Y.
    • Journal Title

      PLOS Pathogens

      Volume: 15(7) Issue: 7 Pages: e1007919-e1007919

    • DOI

      10.1371/journal.ppat.1007919

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic Compatibility of Reassortants between Avian H5N1 and H9N2 Influenza Viruses with Higher Pathogenicity in Mammals.2019

    • Author(s)
      Arai Y, Ibrahim MS, Elgendy EM, Daidoji T, Ono T, Suzuki Y, Nakaya T, Matsumoto K, Watanabe Y.
    • Journal Title

      J Virol.

      Volume: 93(4) Issue: 4

    • DOI

      10.1128/jvi.01969-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of H5N1 influenza virus quasispecies with adaptive hemagglutinin mutations from single-virus infections of human airway cells2018

    • Author(s)
      1.Watanabe Y**, Arai Y, Kawashita N, Ibrahim MS, Elgendy EM, Daidoji T, Kajikawa J, Hiramatsu H, Sriwilaijaroen N, Ono T, Takagi T, Takahashi K, Shioda T, Matsumoto K, Suzuki Y, Nakaya T
    • Journal Title

      J Virol.

      Volume: 印刷中 Issue: 11

    • DOI

      10.1128/jvi.02004-17

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates2018

    • Author(s)
      Arai Y, Kawashita N, Hotta K, Hoang PVM, Nguyen HLK, Nguyen TC, Vuong CD, Le TT, Le MTQ, Soda K, Ibrahim MS, Daidoji T, Takagi T, Shioda T, Nakaya T, Ito T, Hasebe F, Watanabe Y.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 13066-13066

    • DOI

      10.1038/s41598-018-31397-3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Accumulation of PA mutations in Egyptian H5N1 viruses during viral evolution conferred the increased replication ability.2019

    • Author(s)
      Yasuha Arai, Emad M. Elgendy, Tomo Daidoji, Madiha S. Ibrahim, Takaaki Nakaya, Yohei Watanabe.
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] GENETIC COMPATIBILITY AND VIRULENCE OF REASSORTANTS DERIVED FROM H9N2 AND H5N1 AVIAN INFLUENZA VIRUSES CO-CIRCULATING IN EGYPT2018

    • Author(s)
      Yasuha Arai*, Madiha Ibrahim, Takaaki Nakaya, Yohei Watanabe.
    • Organizer
      Negative Strand Virus 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evolutionally dynamics of Egyptian H9N2 avian influenza virus in nature conferred enhanced replication ability in humans.2018

    • Author(s)
      Yasuha Arai*, Madiha S. Ibrahim, Emad M. Elgendy, Tomo Daidoji, Takaaki Nakaya, Yohei Watanabe.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of avian influenza virus infection in human tracheal epithelial cell clones2018

    • Author(s)
      Tomo Daidoji, Junichi Kajikawa, Yohei Watanabe, Yasuha Arai, Takaaki Nakaya.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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