The development of the new therapeutic drug which based on the structure of the virus activation enzyme: The new control method of the highly pathogenic infectious diseases.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09585
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Sagami Women's University
• Principal Investigator: Okumura Yuushi 相模女子大学, 栄養科学部, 教授 (70294725)
• Co-Investigator(Kenkyū-buntansha): 永野 ひかる 大阪府立大学, 公私立大学の部局等, 研究員 (10748924) ; 嶋田 昌子 相模女子大学, 栄養科学部, 教授 (30637369)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 高病原性ウイルス感染症 / ウイルス活性化酵素 / 膜結合型プロテアーゼ / 酵素阻害剤

Outline of Final Research Achievements

Cleavage of viral envelope glycoprotein, hemagglutinin (HA), by host cellular proteases is essential step for influenza virus to enter into the target cells. We identified that ubiquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, were candidates of HA-processing proteases of diverse highly pathogenic avian influenza (HPAI) viruses. In addition, we succeeded to reveal the crystal structure of MSPL/TMPRSS13. In this study, based on their structure, we first generated specific inhibitors for MSPL/TMPRSS13. To confirm the involvement of these proteases in HPAI virus infection, highly virulent virus (A/Crow/Kyoto/53/2004 (H5N1)) was infected into MSPL/TMPRSS13 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. In vivo infectious experiments using their specific inhibitors are currently being investigated.

Free Research Field

生化学・分子生物学・ウイルス学