| Project/Area Number |
21390226
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SAKAMOTO Naoya 東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座教員 (10334418)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Mina 東京医科歯科大学, 医学部附属病院, 助教 (30401342)
AZUMA Seishin 東京医科歯科大学, 医学部附属病院, 助教 (10376783)
WATANABE Mamoru 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10175127)
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| Co-Investigator(Renkei-kenkyūsha) |
FUJITA Megumi (TASAKA Megumi) 東京医科歯科大学, 大学院・医歯学総合研究科, 特任助教 (50510369)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | C型肝炎 / レプリコンシステム / HCV-Feoレプリコン / HCV-JFH1培養系 / 小分子ライブラリー |
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| Research Abstract |
In the present study period, we have conducted high-throughput and comprehensive screening of drugs, physiologically active compounds and small synthetic compounds that suppress HCV replication by using HCV infection and replication cell culture.(1) By using HCV Feo replicon, we conducted cell-based screening of 8, 000 diversity-oriented synthesis(DOS) compounds. We initially selected 41 compounds that suppress HCV replication and further validation identified 5 epoxide compounds that had low IC50.(2) We screened 4, 000 synthetic compounds and identified 5 compounds that suppress HCV replicon and HCV-JFH1 cell culture. We further conducted structure-activity relation(SAR) analyses and identified essential molecular structure for the antiviral activity.(3) We screened serine-rich(SR) protein kinases and identified 4 anti-HCV compounds. By integrating above results, we will further give better understanding of HCV infection life cycle and molecular targets of antiviral activity.
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