Influenza viral hemagglutinin-targeted macrocycles as an antiviral agent
Project/Area Number |
23659238
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Virology
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Research Institution | 公益財団法人東京都医学総合研究所 (2012) Tokyo Metropolitan Organization for Medical Research (2011) |
Principal Investigator |
KOHARA Michinori 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, プロジェクトリーダー (10250218)
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Co-Investigator(Renkei-kenkyūsha) |
MUNAKATA Tubasa 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (50420237)
YASUI Fumihiko 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (40399473)
MUNEKATA Keisuke 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (30569140)
|
Project Period (FY) |
2011 – 2012
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Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 感染防御 / ワクチン / 特殊環状ペプチド / インフルエンザウイルス / HAタンパク質 / 中和活性 / 治療効果 / 抗体医薬 / 低分子ペプチド / HA蛋白質 / ウイルス増殖阻害 |
Research Abstract |
We identified macrocyclic peptides that bind the viral envelope protein hemagglutinin (HA) of influenza A viruses and inhibit its biological function by using the Random non-standard Peptide Integrated Discovery (RaPID) system. The macrocycles inhibited virus replication and exhibited efficacy against viral pneumonia in a mouse model. These results indicate that the RaPID system allows for the development of a new class of HA-targeted antivirals for influenza treatment.
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Report
(3 results)
Research Products
(82 results)
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[Journal Article] Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection2013
Author(s)
Shin-ichiro Nakagawa, Yuichi Hirata, Takeshi Kameyama, Yuko Tokunaga, Yasumasa Nishito, Kazuko Hirabayashi, Junichi Yano, Takahiro Ochiya, Chise Tateno, Yasuhito Tanaka, Masashi Mizokami, Kyoko Tsukiyama-Kohara, Kazuaki Inoue, Makoto Yoshiba, Akinori Takaoka and Michinori Kohara
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Peer Reviewed
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[Journal Article] Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection2013
Author(s)
Nakagawa S, Hirata Y, Kameyama T, Tokunaga Y, Nishito Y, Hirabayashi K, Yano J, Ochiya T, Tateno C, Tanaka Y, Mizokami M, Tsukiyama-Kohara K, Inoue K, Yoshiba M, Takaoka A, Kohara M
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Journal Title
PLoS One
Volume: 8
Issue: 3
Pages: e59611-e59611
DOI
Related Report
Peer Reviewed
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[Journal Article] Hepatitis C virus kinetics by administration of pegylated interferon-α in human and chimeric mice carrying human hepatocytes with variants of the IL28B gene2012
Author(s)
Tsunamasa Watanabe, Fuminaka Sugauchi, Yasuhito Tanaka, Kentaro Matsuura, Hiroshi Yatsuhashi, Shuko Murakami, Sayuki Iijima, Etsuko Iio, Masaya Sugiyama, Takashi Shimada, Masakazu Kakuni, Michinori Kohara, Masashi Mizokami
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[Journal Article] Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver2012
Author(s)
Satoshi Sekiguchi, Kiminori Kimura, Tomoko Chiyo, Takahiro Ohtsuki, Yoshimi Tobita, Yuko Tokunaga, Fumihiko Yasui, Kyoko Tsukiyama-Kohara, Takaji Wakita, Toshiyuki Tanaka, Masayuki Miyasaka, Kyosuke Mizuno, Yukiko Hayashi, Tsunekazu Hishima, Kouji Matsushima and Michinori Kohara
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[Journal Article] Self-enhancement of Hepatitis C Virus Replication by Promotion of Specific Sphingolipid Biosynthesis2012
Author(s)
Yuichi Hirata, Kazutaka Ikeda, Masayuki Sudoh, Akemi Suzuki, Yuko Tokunaga, Leiyun Weng, Masatoshi Ohta, Yoshimi Tobita, Ken Okano, Kazuhisa Ozeki, Kenichi Kawasaki, Takuo Tsukuda, Asao Katsume, Yuko Aoki, Takuya Umehara, Satoshi Sekiguchi, Tetsuya Toyoda, Kunitada Shimotohno, Tomoyoshi Soga, Masahiro Nishijima, Ryo Taguchi, and Michinori Kohara
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Related Report
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[Journal Article] PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication, and induces apoptosis and interferon expression2012
Author(s)
Qiang Wang, Shijian Zhang, Hongbing Jiang, Jinalan Wang, Leiyun, Weng, Yingying Mao, Satoshi Sekiguchi, Fumihiko Yasui, Michinori Kohara, Philippe Buchy, Vincent Deubel, Ke Xu, Bing Sun and Tetsuya Toyoda
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Journal Title
Virology Journal
Volume: 8;9
Pages: 106-118
Related Report
Peer Reviewed
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[Journal Article] An orally available, small-molecule interferon inhibits hepatitis C virus replication2012
Author(s)
Hideyuki Konishi, Koichi Okamoto, Yusuke Ohmori, Hitoshi Yoshino, Hiroshi Ohmori, Motooki Ashiara, Yuichi Hirata, Atsunori Ohta, Hiroshi Sakamoto, Natsuko Hada, Asao Katsume, Michinori Kohara, Kazumi Morikawa, Takuo Tsukuda, Nobuo Shimma, Graham Foster, William Alazawi, Yuko Aoki, Mikio Arisawa, and Masayuki Sudoh
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Journal Title
Sci. Comm
Volume: 2
Pages: 259-259
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[Journal Article] HSC90 is required for nascent hepatitis C virus core protein stability in yeast cells.2012
Author(s)
Kubota N, Inayoshi Y, Satoh N. Fukuda T, Iwai K, Tomoda H, Kohara M, Kataoka K, Shimamoto A, Furuichi Y, Nomoto A, Naganuma A, Kuge S
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Journal Title
FEBS Letters
Volume: (in press)
Issue: 16
Pages: 2318-2325
DOI
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Peer Reviewed
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[Journal Article] Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver.2012
Author(s)
Sekiguchi, S, Kimura K, Chiyo T, Ohtsuki T, Tobita Y, Tokunaga Y, Yasui F, Tsukiyama-Kohara K, Wakita T, Tanaka T, Miyasaka M, Mizuno K, Hayashi Y, Hishima T, Matsushima K and Kohara M.
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Journal Title
PLoS One
Volume: 7
Issue: 12
Pages: e51656-e51656
DOI
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[Journal Article] Monoclonal antibody 2-152a suppresses hepatitis C virus infection through betaine/GABA transporter-12011
Author(s)
Masaaki Satoh, Makoto Saito, Takashi Takano, Yuri Kasama, Tomohiro Nishimura, Yasumasa Nishito, Yuichi Hirata, Masaaki Arai, Masayuki Sudo, Chieko Kai, Michinori Kohara, and Kyoko Tsukiyama-Kohara
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Journal Title
J Infect Dis
Volume: 204(8)
Pages: 1172-80
Related Report
Peer Reviewed
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[Journal Article] Augmentation of DHCR24 expression by hepatitis C virus infection facilitates viral replication in hepatocytes2011
Author(s)
Takashi Takano, Kyoko Tsukiyama-Kohara, Masahiro Hayashi, Yuichi Hirata, Masaaki Satoh, Chise Tateno, Yukiko Hayashi, Tsunekazu Hishima, Nobuaki Funata, Masayuki Sudo, and Michinori Kohara
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Journal Title
J. Hepatology
Volume: 55(3)
Pages: 512-21
Related Report
Peer Reviewed
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