Analysis of respiratory virus activating protease TMPRSS2 and its inhibitor compounds
| Project/Area Number |
18H02665
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49060:Virology-related
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Takeda Makoto 国立感染症研究所, ウイルス第三部, 部長 (40311401)
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| Co-Investigator(Kenkyū-buntansha) |
永田 典代 国立感染症研究所, 感染病理部, 室長 (30270648)
福原 秀雄 北海道大学, 薬学研究院, 准教授 (80707191)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | SARS-CoV-2 / TMPRSS2 / HAI-2 / 新型コロナウイルス / プロテアーゼ / 開裂 / コロナウイルス / 呼吸器ウイルス / ウイルス / 感染症 / トロピズム / インフルエンザウイルス / 中東呼吸器症候群 |
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| Outline of Final Research Achievements |
We have previously shown that the host protease TMPRSS2 activates a wide variety of respiratory viruses and is responsible for the activation of influenza viruses in vivo. In the present study, we analyzed the activation of SARS-CoV-2 by TMPRSS2 and the inhibition of TMPRSS2 and SARS-CoV-2 infection by HAI-2. SARS-CoV-2 infection was markedly enhanced by TMPRSS2 expression. On the other hand, TMPRSS2-mediated SARS-CoV-2 infection was inhibited by HAI-2 in a dose-dependent manner. Knockdown of HAI-2 from cells resulted in a 10-fold increase in the number of viral genome copies detected
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| Academic Significance and Societal Importance of the Research Achievements |
SARS-CoV-2感染症（COVID-19）についてはいまだ有効な治療薬が存在しません。創薬のターゲットを考えるには、ウイルスの増殖機構を分子レベルで詳細に知る必要があります。SARS-CoV-2が効率良く感染するために必要なTMPRSS2という生体内タンパク質分解酵素と、その生理的阻害因子HAI-2の結合様式や作用機序を今後詳細に解析し、いまだ不明な点の多いCOVID-19の病態解明と創薬ターゲット候補の作出へと展開できると考えます。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells2020
Author(s)
Matsuyama Shutoku、Nao Naganori、Shirato Kazuya、Kawase Miyuki、Saito Shinji、Takayama Ikuyo、Nagata Noriyo、Sekizuka Tsuyoshi、Katoh Hiroshi、Kato Fumihiro、Sakata Masafumi、Tahara Maino、Kutsuna Satoshi、Ohmagari Norio、Kuroda Makoto、Suzuki Tadaki、Kageyama Tsutomu、Takeda Makoto
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 117
Issue: 13
Pages: 7001-7003
DOI
Related Report
Peer Reviewed / Open Access
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