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2002 Fiscal Year Final Research Report Summary

Development of Anti-Influenza Drugs of Next Generation Which Conquest Vral Mutation and Inhibit Both Steps of Viral Entry and Release

Research Project

Project/Area Number 13557207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biological pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

SUZUKI Yasuo  University of Shizuoka School of Pharmaceutical Sciences, Biochemistry, Professor, 薬学部, 教授 (00046278)

Co-Investigator(Kenkyū-buntansha) USUI Taichi  University of Shizuoka, Applied Biological Chem., Prof., 農学部, 教授 (50111802)
KANIE Osamu  Mitsubishi Kagaku Inst. Life Sciences, Chief Investigator, 主任研究員
KOBAYASHI Kazukiyo  Nagoya University, Dept. Molecular Design, Prof., 大学院・工学研究科, 教授 (10023483)
レカ ラジュネジャ  太陽化学株式会社, NF事業部, 研究開発・部長
LEKH Raj junejar  Taiyo Kagaku Co. Ltd., Int. Dept., Director
Project Period (FY) 2001 – 2002
KeywordsInfluenza Virus / Anti-Influenza Drug / Hemagglutinin / Nueraminedase / Anti-Viral Drugs / Receptor / Ganglioside / Sensor
Research Abstract

1. The discovery of a new sialocompound which blocks both process of the entry into and release from the host cells of influenza viruses: Neu5Ac3 α F-distearoylphoshatidy lethanolamine in which the C-3 position was modified with an axial fluorine atom, was found to inhibit the catalytic hydrolysis of influenza virus sialidase and the binding activity of hemagglutinin. The inhibitory activities to sialidases were independent of virus isolated examined. The study suggested that the compound is a bew class of bifunctional drug candidates for the future chemotherapy of influenza.
2. Tris-bipyridine ruthenium-complex carrying a disialo complex-type oligosaccharide were prepared via a one-pot transglycosylation using endo-glycosidase (Endo M); they bind to type-A influenza viruses with excellent affinity (IC50 = 8.4 μM), and their luminescence intensity is strongly depressed by virus-binding. This result indicate that the resulting ruthenium-cpmplex is applicable to a new influenza-sensory system.
3. A new sialo-glycosphingolipid (Ganglioside) which binds and strongly inhibits the infection of every human and animal influenza viruses tested was found in and isolated from embryonate chicken eggs. A part of the chemical structure was determined by the analyses of Mass spectrometry. It is suggested that this ganglioside may be one of the real endogenous receptor molecule for influenza viruses in nature. This derivative may applicable to develop a strong anti-influenza drugs in future.
4. Several native and synthesized compounds such as artificial mucin carrying sialyllacto-series sugar chain, or cyclic peptide to which sialyllactose connected were found to inhibit the influenza replication.

  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Kazuhide Totani, Yasuo Suzuki, Kazukiyo Kobayashi, Taichi Usui他: "Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyoligosaccharides with a poly (L-glutamic acid) backbone for inhibition of infection by influenza viruses"Glycobiology. 13(印刷中). (2003)

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  • [Publications] D.Ogawa, K.Shikata, M.Matsuda, S.Okada, J.Wada, S.Yamaguchi, Y.Suzuki, M.Miyasaka: "Preventive effect of sulfated colominic acid on P-selection-dependent infiltration of macrophages on experimentally induced crescentic glomerulonephritis"Clin. Exp. Immunol.. 129. 43-53 (2002)

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  • [Publications] Chao-Tan Guo, Yasuo Suzuki, 他: "An O-glycoside of sialic acid derivative that inhibit both hemagglutinin and sialidase activities of influenza viruses"Glycobiology. 12. 183-190 (2002)

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  • [Publications] M.Matsuda, Yasuo Suzuki他: "Therapeutic effect of suiphated hyaluronic acid, a potential selectin-blocking experimental progressive mesangial proliferative glomerulonephritis"J. Pathol.. 198. 407-414 (2002)

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  • [Publications] R.Komagome, Yasuo Suzuki他: "Oligosaccharides as receptor for JC virus"J. Virol.. 76. 12992-13000 (2002)

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  • [Publications] Yasuo Suzuki: "Glycobiology of influenza virus"Procedings of the 4^<th> Carbohydrate Symposium-Advancement of Glycoscience in the Postgenome Era-Seoul, Nov. 23, 2002, Abstract Book. 2-4 (2002)

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  • [Publications] Yasuo Suzuki: "Sialic acid as the determinant of host range of influenza viruses"Third Pan-Pacific Conference on Sialoglycoscience and Other Novel Forms of Glycosylation Broadbeach, Gold Coast Australia July 14-17, 2002, Abstract book. 31 (2002)

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  • [Publications] Yasuo Suzuki: "Approach to develop new anti-influenza grugs targeted to the function of hemagglutinin and neuraminidase"The first European Conference of Influenza, St Julians, Malta 20-23 Oct. 2002, Abstract Book. 20 (2002)

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  • [Publications] 鈴木康夫: "インフルエンザウイルスの受容体と宿主変異の分子機構"ウイルス(日本ウイルス学会). 51(2). 193-200 (2002)

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  • [Publications] 鈴木康夫: "インフルエンザと糖鎖(Influenza and Sugar Chains)"The Lung perspectives. 10(2). 194-201 (2002)

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  • [Publications] 小島慎司, 長谷川輝明, 米村享宏, 佐々木 賢, 牧村 裕, 山本憲二, 鈴木隆, 鈴木康夫, 小林一清: "ウイルスセンサーを目指した蛍光性糖クラスター化合物の酵素合成と機能評価"日本化学会春季年会、要旨集2002.3.26-29. (2002)

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  • [Publications] Yasuo Suzuki: "Recent Advances in Influenza Virus Res 2002., Ed., Y. Hayase"Research Signpost. 185 (2002)

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  • [Publications] 鈴木康夫, 宮本大誠: "茶成分の抗インフルエンザウイル効果 茶の機能-生態機能の新たな可能性"村松敬一郎、小國伊太郎、伊勢村護、杉山公男、山本(前田)万里遍、学会出版センター. 426 (2002)

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  • [Publications] Tadanobu Takahasi., Takashi Suzuki., Kazuya I.-P., Jwa Hidari., Daisei Miyamoto., Yasuo Suzuki.: "A molecular mechanism for the low-pH actability of sialidase activity of influenza A virus N2 neuraminidase"FEBS LETT., In press. (2003)

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  • [Publications] Shinji Kojima., Teruaki Hasegawa., Takahiro Yonemura., Ken Sasaki., Kenji Yamamoto., Yutaka Makimura., Tadanobu Takahashi., Takashi Suzuki., Yasuo Suzuki., Kasukiyo Kobayashi.: "Ruthenium complexes carrying a disialo complex-type oligosaccharide: enzymatic synthesis and its application to a luminescent probe to defect influenza viruses"Chem. Comm. DOI:10.1039/b210739b, The Royal Society of Chemistry, Advance Article. (2003)

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  • [Publications] Yuko Matsushima-Hibiya., Masahiko Watanabe., Kazuya Hidari., Daisei Miyamoto., Yasuo Suzuki., Takeshi Kasama., Takashi Kanazawa., Kotaro Koyama., Takashi Sugimura., Keiji Wakabayashi.: "Identification of glycosphingolipid receptors for pierisin-1, a guanine-specific ADP-ribosylating toxin from the cabbage butterfly"J. Biol. Chem.. 278. 9972-9978 (2003)

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  • [Publications] Kazuhide Totami., Takeshi Kubota., Takao Huroda., Takeomi Murata., Kazuya I.-P. Jwa Hidari., Takashi Suzuki., Yasuo Suzuki., Kazukiyo Kobayashi., Hisashi Ashida., Kenji Yamamoto., and Taichi Usui.: "Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyloligosaccharides with a poly(L-glutamic acid) backbone for inhibition of infection by influenza viruses"Glycobiology. 13(5). 315-326 (2003)

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  • [Publications] Mitsuhiro Matsuda., Kenichi Shikata., Fujio Shimizu., Yasuo Suzuki., Masayuki Miyasaka., Hiroshi Kawachi., Hiroto Kawashima., Jun Wada., Hikaru Sugimoto., Yasushi Shikata., Daisuke Ogawa., Shinichiro J. Tojo., Kazuo Akima., Hirofumi Makino.: "Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis"J. Pathol.. 198. 407-414 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Rika Komagome., Hirofumi Sawa., Takashi Suzuki., Yasuo Suzuki., Shinya Tanaka., Walter J. Atwood., Kazuo Nagashima.: "Oligosaccharides as receptor for JC virus"J. Virol.. 76. 12992-13000 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D.Ogawa., K.Shikata., M.Matsuda., S.Okada., J.Wada., S.Yamaguchi., Y.Suzuki., M.Miyasaka.: "Preventive effect of sulfated colominic acid on P-selectin-dependent infiltration of macrophages on experimentally induced crescentic glomerulonephritis"Clin. Exp. Immuno.. 129. 43-53 (2002)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Chao-Tan Guo., Xue-Long Sun., Osamu Kanie., Kennedy Francis Shoutridge., Takashi Suzuki., Daisei Miyamoto., Kazuya I.-P. Jwa Hidari., Chi-Huey Wong, and Yasuo Suzuki.: "An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses"Glycobiol.. 12. 183-190 (2002)

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  • [Publications] Kamuruddlin Ahmed., Yasuo Suzuki., Daisei Miyamoto., Tsuyoshi Nagatake.: "Asialo-GM1 and Asialo-GM2 are putative adhesion molecules for Moraxella catarrhalis"Med. Microbiol. Immunol.. 191. 5-10 (2002)

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  • [Publications] Hughes MT., McGregor M., Suzuki T., Suzuki Y., Kawaoka Y.: "Adaptation of influenza A viruses to cells expressing low levels of sialic acid leads neuraminidase activity"J. Virol.. 75(8). 3766-3770 (2001)

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  • [Publications] Masafumi Kimura., Kazuya I.-P. Jwa Hidari., Takashi Suzuki., Daisei Miyamoto., Yasuo Suzuki.: "Engagement of endogenous ganglioside Gmla induces tyrosine phosphorylation involved in neuron-like differentiation of PC12 cells"Glycobiology. 11(4). 335-343 (2001)

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  • [Publications] Kiyoshi Ikeda., Kimihiko Sano., Masaki Ito., Kazuya idari., Takashi Suzuki., Yasuo Suzuki., Kiyoshi Tanaka.: "Synthesis of 2-deoxy-2, 3-didehydro-N-acetylneuraminic acid nalogues modified at the C-4 and C-9 positions and their behavior towards sialidase from influenza virus and pig liver membrene"Carbohydrate Res.. 330. 31-41 (2001)

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  • [Publications] Takashi Suzuki., Allen Portner., Ruth Ann Scroggs., Makoto Uchikawa., Noriko Koyama., Kazuko Matsuo., Yasuo Suzuki., Toru Takimoto.: "Receptor specificities of human respiroviruses"J. Virol.. 75(10). 46-4-4613 (2001)

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  • [Publications] Takashi Suzuki., Kiyoshi Ikeda., Noriko Koyama., Chika Hosokawa., Toshuhiro Kogure., Tadanobu Takahashi., Kazuya I.-P. Jwa Hidari., Daisei Miyamoto., Kiyoshi Tanaka., Yasuo Suzuki.: "Inhibition of human parainfluenza virus type 1 sialidase by analogs of 2-deoxy-2, 3-didehydro-N-acetylneuraminic acid"Glycoconjugate J.. 18. 331-337 (2001)

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  • [Publications] Tadanobu Takahashi., Yasuo Suzuki., Daisuke Nishimura., Nana Kawase., Yukiko Kobayashi., Kazuya I.-P. Jwa Hidari., Daisei Miyamoto., Chao Tan Guo., Kennedy F. Shortridge., Takashi Suzuki.: "Duck and Human Pandemic Influenza A viruses retain sialidase activity in Low pH conditions"J. Biochem.. 130(2). 279-283 (2001)

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  • [Publications] Chao-Tan Guo., Shinji Ohta., Akihiro Yoshimoto., Kuniho Nakata., Kennedy F. Shortridge., Tadanobu Takahashi., Takashi Suzuki., Daisei Miyamoto., Kazuya I.-P. Iwa Hidari., Yasuo Suzuki.: "A unique phosphatidylinositol bearing a novel branched-chain fatty acid from Rhodococcus equi binds to influenza virus hemagglutinin and inhibits the infection of cells"J. Biochem. 130. 377-384 (2001)

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  • [Publications] Takehiko Saito., Wilina Lim., Takashi Suzuki., Yasuo Suzuki., Hiroshi Kida., Shin-Ichiro Nishimura., Masato Tashiro.: "Characterization of a human H9N2 influenza virus isolated in Hong Kong"Vaccine. 20(1-2). 125-133 (2001)

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  • [Publications] Yasuo Suzuki., Ed., Y.Hayase.: "Reseptor binding specificity and host range variation of influenza viruses (Review), Recent Advances in Influenza Virus Res 2002"Research Signpost. 161-168 (2002)

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  • [Publications] Yasuo Suzuki., Toshihiro Ito., Takashi Suzuki., Daisei Miyamoto., Kazuya I.-P. J. Hidari., Chao-Tan Guo., Hiroshi Kida., Robert G. Webster., Thomas M. Chambers., Yoshihiro Kawaoka., Ed. A. Osterhaus., N.Cox., A.Hampson.: "Sialyl sugar chains as receptor and determinants of host range of influenza A viruses, Options for the control of Influenza IV, 1219"Excerpta Media International Congress Series Published Elsevier Science B.V.. 521-525 (2001)

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Published: 2004-04-14  

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