Analysis of respiratory virus activating protease TMPRSS2 and its inhibitor compounds

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02665
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Takeda Makoto 国立感染症研究所, ウイルス第三部, 部長 (40311401)
• 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)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: SARS-CoV-2 / TMPRSS2 / HAI-2

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

Free Research Field

ウイルス学

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。