| Project/Area Number |
18K08453
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | Sagami Women's University |
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Principal Investigator |
Okumura Yuushi 相模女子大学, 栄養科学部, 教授 (70294725)
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| Co-Investigator(Kenkyū-buntansha) |
嶋田 昌子 相模女子大学, 栄養科学部, 教授 (30637369)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 高病原性鳥インフルエンザウイルス / ウイルス活性化酵素 / 膜結合型プロテアーゼ / プロテアーゼ阻害剤 / 高病原性感染症 / 膜結合型酵素 / 酵素特異的阻害剤 / 治療薬 |
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| Outline of Final Research Achievements |
Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases. We identified that ubiquitous type II transmembrane serine proteases, MSPL, were candidates of HA-processing proteases for highly pathogenic avian influenza (HPAI) viruses. In addition, we succeeded to solve the crystal structure of MSPL. In this study, based on the structure of MSPL, we first generated specific inhibitors for MSPL. To confirm the involvement of these proteases in HPAI virus infection, highly virulent virus (A/Crow/Kyoto/53/2004 (H5N1)) was infected into MSPL stably expressed cells with or without their specific inhibitors. As a result, we concluded that these proteases specific inhibitors might be suppress HPAI virus multicycle replication and spreading. Furthermore, based on the structure of MSPL, we also constructed a homology model of TMPRSS2. The model may provide the structural insight for the drug development for COVID-19.
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| Academic Significance and Societal Importance of the Research Achievements |
高病原性ウイルスの感染メカニズムにおいて、感染時における宿主側のウイルス活性化酵素を同定できたこと、およびその酵素の立体構造を決定し、酵素特異的阻害剤を開発できたことは、ウイルスが、宿主側のどのような因子を利用して感染・増殖するのかを明らかにしたことを意味し、学術的意義は大きい。同時に、酵素特異的阻害剤が高病原性ウイルス感染症を制御し得ることを証明した事実は、高病原性ウイルス感染症に対する新たな制御法（予防・治療法）の獲得につながり、社会的意義は計り知れない。
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