| Project/Area Number |
25450417
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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 | Hokkaido University |
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Principal Investigator |
Igarashi Manabu 北海道大学, 人獣共通感染症リサーチセンター, 准教授 (10374240)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKADA AYATO 北海道大学, 人獣共通感染症リサーチセンター, 教授 (10292062)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | インフルエンザ / ウイルス / 抗体 / 計算科学 / 分子動力学 / 分子モデリング / 分子動力学計算 / 分子間相互作用 / ホモロジーモデリング |
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| Outline of Final Research Achievements |
The HA of influenza A viruses is classified into 16 subtypes (H1-H16). We have previously reported a cross-reactive antibody, designated S139/1, which neutralizes H1, H2, H3, H13, and H16 subtypes. In this study, we characterized the S139/1 recognition sites on different HAs by computational methods such as molecular modeling and dynamics simulations. We investigated the contribution of individual residues on each HA to the interaction with S139/1, and found that amino acids at 10 positions on HA strongly contributed to S139/1 binding as for the strains neutralized by S139/1. Analysis of hydrogen bond interactions emphasized that the residues at positions 156, 158 and 193 were the most important for S139/1 binding. Indeed, amino acid substitutions at these three positions were experimentally observed in the mutant viruses escaping from neutralization by S139/1. Thus, our computational methods identified the amino acid residues critical for the cross-neutralizing activity of S139/1.
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