| Project/Area Number |
16K08032
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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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| Research Field |
Veterinary medical science
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| Research Institution | Nippon Veterinary and Life Science University |
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Principal Investigator |
Ujike Makoto 日本獣医生命科学大学, 獣医学部, 准教授 (50415478)
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| Co-Investigator(Kenkyū-buntansha) |
袴田 航 日本大学, 生物資源科学部, 准教授 (10333337)
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| Research Collaborator |
Matsuyama Shutoku
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | コロナウイルス / 抗ウイルス薬 / 小胞体αグルコシダーゼ阻害薬 / ウイルス学 / 新規糖鎖付加阻害薬 |
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| Outline of Final Research Achievements |
Endoplasmic reticulum (ER) alpha-glucosidase inhibitors (AGI) inhibit host ER alpha-glucosidases, resulting in the suppression of host glycoprotein synthesis. Because most enveloped viruses including coronavirus (CoV) contain glycoproteins, AGI would efficiently disrupt the morphogenesis of a broad spectrum of enveloped viruses in infected cells. In this study, we identified six novel AGIs which have a novel framework by screening from the compound library and found that these AGIs showed strong antiviral activity against animal or human CoVs. It was first thought that the anti-CoV activity by novel AGIs was due to the inhibition of the structural protein, viral spike glycoproteins. However, we found that novel AGIs specifically inhibited not only spike glycoprotein but viral non-glycoproteins and even viral transcription activity. These data suggested that novel AGIs showed anti-CoV activity by a distinct mechanism from conventional one.
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| Academic Significance and Societal Importance of the Research Achievements |
CoV科は、監視伝染病である豚伝染性胃腸炎及び伝染性気管支炎ウイルスや、近年国内で大流行した豚流行性下痢ウイルス、実験動物取扱時に問題となるマウス肝炎ウイルス、ペットの猫や野生ネコ属に致死的な病態を引き起こす猫伝染性腹膜炎ウイルスを含む。また、ヒトにおいては高い致死率をもつ重症呼吸器症候群や中東呼吸器症候群CoVを含み医学・獣医学領域で重要なウイルスである。しかしながら、現在でも効果的な抗CoV薬は存在しない。本研究により見出された、幅広いCoVに効果をもつAGIsが臨床応用されれば動物の衛生及びヒトの公衆衛生に大きな影響を与えると考えられる。
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