• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Theory for effective antiviral strategy based on multiscale mathematical modeling

Research Project

Project/Area Number 15KT0107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Mathematical Sciences in Search of New Cooperation
Research InstitutionKyushu University

Principal Investigator

Iwami Shingo  九州大学, 理学研究院, 准教授 (90518119)

Co-Investigator(Kenkyū-buntansha) 中岡 慎治  東京大学, 生産技術研究所, 派遣研究員 (30512040)
Research Collaborator NAKAOKA SHINJI  
Project Period (FY) 2015-07-10 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords数理モデル型アプローチ / 定量的データ解析 / マルチスケールモデル / 多階層数理モデル / 偏微分方程式 / データ解析 / 数理モデル / 融合研究 / 構造化個体群モデル / ウイルス感染実験
Outline of Final Research Achievements

In the current era of antiviral drug therapy, combining multiple drugs is a primary approach for improving antiviral effects, reducing the doses of individual drugs, relieving the side effects of strong antiviral drugs, and preventing the emergence of drug-resistant viruses. Mathematical models of viral infection dynamics provide an ideal tool for this purpose. By combining the mathematical modeling of virus dynamics with drug combination theories, we could show the principles by which drug combinations yield a synergistic effect.

Academic Significance and Societal Importance of the Research Achievements

現在、ウイルス感染症やがんなどの治療において、複数の薬剤を組み合わせる「多剤併用治療」が積極的に行われている。これは、治療効果の増幅に加えて、薬剤耐性の出現リスクや副作用、治療費の軽減を目的としている。しかし、これまでの薬剤組み合わせは、実験や治験の成果などを基に、経験的に行われてきた。本研究では、数理モデルを援用する事で、多剤併用治療の最適化を実現する理論を構築し、新しい薬学分野を開拓した。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (59 results)

All 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (17 results) Journal Article (26 results) (of which Int'l Joint Research: 20 results,  Peer Reviewed: 25 results,  Open Access: 17 results,  Acknowledgement Compliant: 6 results) Presentation (14 results) (of which Int'l Joint Research: 14 results,  Invited: 7 results) Book (2 results)

  • [Int'l Joint Research] INSERM(フランス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] UNSW(オーストラリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ICL(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ロスアラモス国立研究所(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] INSERM(フランス)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] ライルソン大学(カナダ)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] ニューサウスウェールズ大学(オーストラリア)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] ライルソン大学(カナダ)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] ロスアラモス国立研究所(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] ユトレヒト大学(オランダ)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] ニューサウスウェールズ大学(オーストラリア)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] ハイデルベルグ大学(ドイツ)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] INSERM(France)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Ryerson University(Canada)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Utrecht University(オランダ)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Loa Alamos National Laboratory(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Epidermal growth factor receptor is a host entry cofactor triggering hepatitis B virus internalization2019

    • Author(s)
      M. Iwamoto, W. Saso, R. Sugiyama, K. Ishii, M. Ohki, S. Nagamori, R. Suzuki, H. Aizaki, A. Ryo, J-H Yun, S-Y Park, N. Ohtani, M. Muramatsu, S. Iwami, Y. Tanaka, C. Sureau, T. Wakita and K. Watashi
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 116 Issue: 17 Pages: 8487-8492

    • DOI

      10.1073/pnas.1811064116

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mathematical analysis of a transformed ODE from a PDE multiscale model of hepatitis C virus infection2019

    • Author(s)
      Kitagawa K., Kuniya T., Nakaoka S., Asai Y., Watashi K. and Iwami S.
    • Journal Title

      Bulletin of Mathematical Biology

      Volume: 81(5) Issue: 5 Pages: 1427-1441

    • DOI

      10.1007/s11538-018-00564-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative immunology by data analysis using mathematical models2019

    • Author(s)
      S. Iwanami and S. Iwami
    • Journal Title

      Encyclopedia of Bioinformatics and Computational Biology

      Volume: 2 Pages: 984-992

    • DOI

      10.1016/b978-0-12-809633-8.20250-1

    • ISBN
      9780128114322
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection2018

    • Author(s)
      Y. Ito, A. Tauzin, A. Remion, K. Ejima, F. Mammano and S. Iwami
    • Journal Title

      Journal of Theoretical Biology

      Volume: 455 Pages: 39-46

    • DOI

      10.1016/j.jtbi.2018.06.025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A PDE multiscale model of hepatitis C virus infection can be transformed to a system of ODEs2018

    • Author(s)
      K. Kitagawa, S. Nakaoka, Y. Asai, K. Watashi, S. Iwami
    • Journal Title

      Journal of Theoretical Biology

      Volume: 48 Pages: 80-85

    • DOI

      10.1016/j.jtbi.2018.04.006

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Malaria incidences in South Africa linked to a climate mode in southwestern Indian Ocean2018

    • Author(s)
      SK. Behera, Y. Morioka, T. Ikeda, T. Doi, JV. Ratnam, M. Nonaka, A. Tsuzuki, C. Imai, Y. Kim, M. Hashizume, S. Iwami, P. Kruger, R. Maharaj, N. Sweijd and N. Minakawa
    • Journal Title

      Environmental Development

      Volume: 27 Pages: 47-57

    • DOI

      10.1016/j.envdev.2018.07.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells.2018

    • Author(s)
      Mahgoub M, Yasunaga JI, Iwami S, Nakaoka S, Koizumi Y, Shimura K, Matsuoka M.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 115 Issue: 6 Pages: 529-538

    • DOI

      10.1073/pnas.1715724115

    • NAID

      120006697286

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human-specific adaptations in Vpu conferring anti-tetherin activity are critical for efficient early HIV-1 replication in vivo.2017

    • Author(s)
      Eri Yamada, Shinji Nakaoka, Lukas Klein, Elisabeth Reith, Simon Langer, Kristina Hopfensperger, Shingo Iwami, Gideon Schreiber, Frank Kirchhoff, Yoshio Koyanagi, Daniel Sauter & Kei Sato
    • Journal Title

      Cell Host & Microbe

      Volume: 23 Issue: 1 Pages: 110-120

    • DOI

      10.1016/j.chom.2017.12.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Number of infection events per cell during HIV-1 cell-free infection2017

    • Author(s)
      Ito Y, Remion A, Tauzin A, Ejima K, Nakaoka S, Iwasa Y, Iwami S, Mammano F
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 6559-6559

    • DOI

      10.1038/s41598-017-03954-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally boosting direct-acting antiviral-based treatments.2017

    • Author(s)
      Ohashi HK, Koizumi Y, Fukano K, Wakita T, Perelson AS, Iwami S, Watashi K
    • Journal Title

      Proc Acad Natl Acad USA

      Volume: 114 Issue: 23

    • DOI

      10.1073/pnas.1705234114

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation.2017

    • Author(s)
      Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S. Harris, Yoshio Koyanagi & Kei Sato
    • Journal Title

      PLOS Pathogens

      Volume: 13 Issue: 5 Pages: 31-31

    • DOI

      10.1371/journal.ppat.1006348

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture2017

    • Author(s)
      Iwanami S, Kakizoe Y, Morita S, Miura T, Nakaoka S, Iwami S
    • Journal Title

      Theor Biol Med Model

      Volume: 14 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s12976-017-0055-8

    • NAID

      120006305768

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation and cellular communication2017

    • Author(s)
      Fujiu K, Shibata M, Nakayama Y, Ogata F, Matsumoto S, Noshita K, Iwami S, Nakae S, Komuro I, Nagai R, Manabe I
    • Journal Title

      Nature Medicine

      Volume: 印刷中 Issue: 5 Pages: 611-622

    • DOI

      10.1038/nm.4326

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection2017

    • Author(s)
      Y. Koizumi, H. Ohashi, S. Nakajima, Y. Tanaka, T. Wakita, AS. Perelson, S. Iwami†, and K. Watashi†.
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: 114 Pages: 1922-1927

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Duration of SHIV production by infected cells is not exponentially distributed: Implications for estimates of infection parameters and antiviral efficacy2017

    • Author(s)
      CA. Beauchemin, T. Miura, and S. Iwami
    • Journal Title

      Scientific Reports

      Volume: 7 Pages: 42765-42765

    • NAID

      120005997746

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation and cellular communication2017

    • Author(s)
      K. Fujiu†, M. Shibata†, Y. Nakayama, F. Ogata, S. Matsumoto, K. Noshita, S. Iwami, S. Nakae, I. Komuro, R. Nagai, and I. Manabe
    • Journal Title

      Nature Medicine

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] (In)validating experimentally-derived knowledge about influenza A defective interfering particles2016

    • Author(s)
      LE. Liao, S. Iwami, CA. Beauchemin.
    • Journal Title

      Journal of the Royal Society Interface

      Volume: 13 Pages: 20160412-20160412

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of asymptomatic infections on the early spread of malaria2016

    • Author(s)
      T. Funo, H. Inaba, M. Jusup, A. Tsuzuki, N. Minakawa, and S. Iwami
    • Journal Title

      Japan Journal of Industrial and Applied Mathematics

      Volume: 33 Pages: 671-681

    • NAID

      210000176097

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Modelling Ebola virus dynamics: Implications for therapy2016

    • Author(s)
      A. Martyushev, S. Nakanoka, K. Sato, T. Noda†, and S. Iwami†.
    • Journal Title

      Antiviral Research

      Volume: 135 Pages: 61-73

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model2016

    • Author(s)
      H. Ikeda†, S Nakaoka†, RJ. De Boer, S. Morita, N. Misawa, Y. Koyanagi, K. Aihara, K. Sato‡, and S. Iwami‡
    • Journal Title

      Retrovirology

      Volume: 13 Pages: 2-2

    • NAID

      120006353849

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamics of HIV infection in lymphoid tissue network2016

    • Author(s)
      S. Nakaoka, S. Iwami, and K. Sato
    • Journal Title

      Journal of Mathematical Biology

      Volume: 72 Pages: 909-938

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Journal Article] Quantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model2016

    • Author(s)
      H. Ikeda, S Nakaoka, RJ. De Boer, S. Morita, N. Misawa, Y. Koyanagi, K. Aihara, K. Sato, and S. Iwami
    • Journal Title

      Retrovirology

      Volume: -

    • NAID

      120006353849

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Comment: Dynamically rich, yet parameter-sparse models for spatial epidemiology Comment on “Coupled disease-behavior dynamics on complex networks: A review”by Z. Wang et al.2015

    • Author(s)
      M. Jusup, S. Iwami, B. Podobnik, and E. Stanley
    • Journal Title

      Physics of Life Reviews

      Volume: 15 Pages: 43-46

    • DOI

      10.1016/j.plrev.2015.09.006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Exploring the conserved quantity of viral infection model with periodical cell removal2015

    • Author(s)
      Y. Kakizoe, and S. Iwami
    • Journal Title

      Japan Journal of Industrial and Applied Mathematics

      Volume: 32 Pages: 1-9

    • NAID

      210000180589

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cell-to-cell infection by HIV contributes over half of virus infection2015

    • Author(s)
      Shingo Iwami, Junko S. Takeuchi, Shinji Nakaoka, Fabrizio Mammano, François Clavel, Hisashi Inaba, Tomoko Kobayashi, Naoko Misawa, Kazuyuki Aihara, Yoshio Koyanagi & Kei Sato
    • Journal Title

      eLife

      Volume: 4 Pages: 1-16

    • DOI

      10.7554/elife.08150

    • NAID

      120005997708

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin2015

    • Author(s)
      Shingo Iwami, Kei Sato, Satoru Morita, Hisashi Inaba, Tomoko Kobayashi, Junko S. Takeuchi, Yuichi Kimura, Naoko Misawa, Fengrong Ren, Yoh Iwasa, Kazuyuki Aihara & Yoshio Koyanagi
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 12256-12256

    • DOI

      10.1038/srep12256

    • NAID

      120005774579

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection2018

    • Author(s)
      Shingo Iwami
    • Organizer
      ECMTB2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PKPDVD modeling for multi-drug treatment on HCV infection2018

    • Author(s)
      Shingo Iwami
    • Organizer
      KSIAM2018SMB
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Characterizing SHIV infection in vitro and in vivo2018

    • Author(s)
      Shingo Iwami
    • Organizer
      &JSMB2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Quantification of virus infection in cell culture2017

    • Author(s)
      Shingo Iwami
    • Organizer
      A3-NIMS joint workshop on mathematical biology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Quantifying antiviral activity optimizes drug combinations against HCV infection2017

    • Author(s)
      Shingo Iwami
    • Organizer
      The 18th RIES-HOKUDAI international symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Modeling virus infection in cell culture2017

    • Author(s)
      Shingo Iwami
    • Organizer
      Simons Semester on Mathematical Biology in Warsaw, Epi-workshop
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] HCV entry inhibitors for optimally boosting direct-acting antiviral-based treatments2017

    • Author(s)
      Shingo Iwami
    • Organizer
      Innovative Mathematical Modeling for the Analysis of Infectious Disease Data
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Modeling ebola virus dynamics Implications for therapy2015

    • Author(s)
      Shingo Iwami
    • Organizer
      Innovative Mathematical Modeling for the Analysis of Infectious Disease Data
    • Place of Presentation
      Sapporo
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Quantifying antiviral activity optimizes drug combinations against HCV infection2015

    • Author(s)
      Shingo Iwami
    • Organizer
      HCV 2015
    • Place of Presentation
      France
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Modeling ebola virus dynamics Implications for therapy2015

    • Author(s)
      Shingo Iwami
    • Organizer
      Erice MatheCompEpi2015
    • Place of Presentation
      Italy
    • Year and Date
      2015-08-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A conserved quantity of virus infection in cell culture2015

    • Author(s)
      Shingo Iwami
    • Organizer
      JSMB-CJK
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-08-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Modeling ebola virus dynamics Implications for therapy2015

    • Author(s)
      Shingo Iwami
    • Organizer
      JSMB-CJK
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-08-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Quantifying the antiviral effect of IFN on HIV-1 replication in cell culture2015

    • Author(s)
      Shingo Iwami
    • Organizer
      JSMB-CJK
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-08-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Quantifying combination activity of anti-HCV drugs in vitro2015

    • Author(s)
      Shingo Iwami
    • Organizer
      2nd WORKSHOP ON VIRUS DYNAMICS
    • Place of Presentation
      Canada
    • Year and Date
      2015-07-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 日本生態学会編 シリーズ現在の生態学 6巻 「感染症の生態学」 “第23章 AIDS”2016

    • Author(s)
      岩見真吾
    • Total Pages
      11
    • Publisher
      共立出版
    • Related Report
      2015 Research-status Report
  • [Book] 日本生態学会編 シリーズ現在の生態学 1巻 「集団生物学」 “第5章 感染症動態”2015

    • Author(s)
      岩見真吾
    • Total Pages
      13
    • Publisher
      共立出版
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-07-14   Modified: 2022-02-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi