| Project/Area Number |
16590434
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | University of Toyama (2005-2006)
Toyama Medical and Pharmaceutical University (2004) |
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Principal Investigator |
HAYASHI Kyoko University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences, Assistant professor, 医学薬学研究部, 助教 (60110623)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Toshimitsu University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences, Professor, 医学薬学研究部, 教授 (40092796)
LEE Jung-bum University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences, Assistant professor, 医学薬学研究部, 助教 (40332655)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | human coronavirus / glycoproteins / monoclonal antibody / antiviral assay / ヒトコロナウイルス / 糖蛋白質 / ウイルス活性 / 作用標的 |
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| Research Abstract |
More than three hundreds of substances including synthesized chemicals and natural products from plants and algae have been assayed for their anti-huma coronavirus (HCoV) activities. Some sulfated polysaccharides isolated from algae showed potent antiviral activity. Other classes of substance with low molecular weight also showed higher antiviral action. In order to elucidate their anti-HCoV targets, we have performed different kinds of experiments and obtained the results as shown below.
1. Effect on viral adsorption to host cells : At the first step of viral replication, virus binds to the receptor present on host cell membrane. All the substances with potent anti-HCoV activity were found not to interfere with the binding step.
2. Effect on viral penetration into host cells : After binding to host cells, virus particles rapidly penetrate into the cells. Anti-HCoV agents including rhamnan sulfate, dextran sulfate, digitoxin, digoxin, and bufalin showed inhibitory effect on the penetration of HCoV in the range of antiviral concentrations.
3. Virucidal activity : Direct inactivity of virus infectivity should attribute to the suppression of HCoV replication at the respiratory organs. So far, a derivative of phenoxazines showed potent virucidal activity without cytotoxicity. The elucidation of the mechanism of this action is in progress.
4. Effect on the synthesis of HCoV-specific proteins : Virus-specific proteins were detected by immunoblotting using the monoclonal antibodies. A natural rhamnan sulfate isolated from an edible alga suppressed efficiently the viral protein synthesis when added to the medium at the same time as viral infection.
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