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A computational structural study on recognition of the influenza virus hemagglutinin by hterosubtypic monoclonal antibody

Research Project

Project/Area Number 17K08069
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Veterinary medical science
Research InstitutionHokkaido University

Principal Investigator

Igarashi Manabu  北海道大学, 人獣共通感染症国際共同研究所, 准教授 (10374240)

Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsインフルエンザウイルス / 抗体 / 分子動力学 / 分子モデリング / 分子間相互作用 / 結合自由エネルギー / 親和性 / インフルエンザ / ウイルス / 分子動力学計算 / 分子設計 / 計算科学
Outline of Final Research Achievements

We are aiming to design a neutralizing antibody against escape mutant strains and/or multiple HA subtypes of influenza A viruses. In this study, we tried to modify the binding ability of S139/1, a cross-reactive neutralizing monoclonal antibody against HAs, using the binding free energy obtained from molecular dynamics simulations as an indicator. For the HA from A/Victoria/3/75 (H3N2) used in this study, only amino acid substitutions on S139/1 was unable to restore the recogniton ability of S139/1 against escape mutants, suggesting that the replacement of an entire CDR loop are required.

Academic Significance and Societal Importance of the Research Achievements

本研究の最終目的は、抗体の親和性・特異性を制御するための論理的分子設計手法の確立である。このような立体構造を基盤に既存抗体の親和性・特異性を改変する技術は、様々な人獣共通感染症の診断・治療研究へ幅広く応用されることが想定される。本課題の成果はその設計手法の一助となると考えられる。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (10 results)

All 2019 2018 2017 Other

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

  • [Journal Article] Generation of bat-derived influenza viruses and their reassortants2019

    • Author(s)
      Sato Masahiro、Maruyama Junki、Kondoh Tatsunari、Nao Naganori、Miyamoto Hiroko、Takadate Yoshihiro、Furuyama Wakako、Kajihara Masahiro、Ogawa Hirohito、Manzoor Rashid、Yoshida Reiko、Igarashi Manabu、Takada Ayato
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1158-1158

    • DOI

      10.1038/s41598-018-37830-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural Characterization of Pan-Ebolavirus Antibody 6D6 Targeting the Fusion Peptide of the Surface Glycoprotein2018

    • Author(s)
      Milligan Jacob C、Parekh Diptiben V、Fuller Katherine M、Igarashi Manabu、Takada Ayato、Saphire Erica Ollmann
    • Journal Title

      The Journal of Infectious Diseases

      Volume: 219 Issue: 3 Pages: 415-419

    • DOI

      10.1093/infdis/jiy532

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influenza A Virus M2 Protein: Roles from Ingress to Egress2017

    • Author(s)
      Manzoor Rashid、Igarashi Manabu、Takada Ayato
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 12 Pages: 2649-2649

    • DOI

      10.3390/ijms18122649

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Mechanisms of antibody-mediated protection against H5N1 influenza virus infection2018

    • Author(s)
      Reiko Yoshida, Ema Qurnianingsih, Rashid Manzoor, Mari Ishijima, Asako Shigeno, Hiroko Miyamoto, Manabu Igarashi, Chairul A Nidom, Ayato Takada
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ウイルス蛋白質と宿主分子の 相互作用解析:立体構造情報の活用2018

    • Author(s)
      五十嵐 学
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ウイルス蛋白質と宿主分子の相互作用解析 : 計算科学の活用2017

    • Author(s)
      五十嵐 学
    • Organizer
      CBI学会2017年大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Computational characterization of influenza A virus hemagglutinin recognition sites by a cross-neutralizing monoclonal antibody2017

    • Author(s)
      五十嵐学、関嶋政和、安尾信明、阿部貴志、Rashid Manzoor、渡部輝明、広川貴次、高田礼人
    • Organizer
      CBI学会2017年大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 計算科学的手法によるウイルスタンパク質の解析2017

    • Author(s)
      五十嵐 学
    • Organizer
      日本生化学会北海道支部、日本生物物理学会北海道支部合同シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] in silico創薬におけるスクリーニングの高速化・高精度化技術2018

    • Author(s)
      五十嵐学、他約80名
    • Total Pages
      540
    • Publisher
      技術情報協会
    • ISBN
      9784861046889
    • Related Report
      2017 Research-status Report
  • [Remarks] 北海道大学人獣共通感染症リサーチセンター国際疫学部門

    • URL

      http://www.czc.hokudai.ac.jp/epidemiol/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2024-01-30  

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