Hemagglutinin mutations responsible for the binding of highly pathogenic influenza virus to human type receptors and influenza drug discovery.

2011 Fiscal Year Final Research Report

• Project/Area Number: 20390028
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Chubu University
• Principal Investigator: SUZUKI Yasuo 中部大学, 生命健康科学部, 教授 (00046278)
• Project Period (FY): 2008 – 2011
• Keywords: インフルエンザウイルス / へマグルチニン / 高病原性鳥インフルエンザウイルス

Research Abstract

During the period(April, 2008.March 2012) of this grant, we clarified several new mechanisms on the hemagglutinin(HA) mutations responsible for the binding of highly pathogenic influenza virus(H5N1 subtype) to human type receptors and got progress on the drug discovery for influenza.
(1) We identified several type of amino acid substitutions in the HA(H5) spike of highly pathogenic avian influenza viruses(H5N1 subtype) isolated from not only "patients" but also from "birds" that increase their human-type receptor(Neu5Acα2, 6Gal) specificity Viruses in those sublineages exhibited increased attachment and infectivity in the human respiratory tract. We also identified an experimental reassortant H5 HA/H1N1 virus. comprising H5 HA(from an H5N1 virus) with only four amino acid mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus. that exhibited increased attachment to the human type receptor and was capable of "droplet transmission in a ferret model". Our findings may help to advance our understanding of the mechanisms and evolutionary pathways that contribute to avian influenza virus transmission in mammals.
(2) We also determined the fine chemical structures of H5N1 viral HA receptor N-linked sialo sugar chains of several target cells of H5N1 host animals, such as pig, dog, cat, embryonated chicken eggs.
(3) We developed more than 15 new synthetic and native compounds which inhibit human influenza virus receptor binding, replication and budding from the infected host cells.

Research Products

• [Journal Article] Antiviral effects of Psidium Guajava Linn.(guava) tea on the growth of clinical isolated H1N1 viruses : its role in viral hemagglutination and neuraminidase inhibition (2012)
  • Author(s): N. Sriwilaijaroen, S. Fukumoto, K, Kumagai, H. Hiramatsu, T. Odagiri, M. Tashiro, Y. Suzuki
  • Journal Title: Antiviral Res Volume: 94(2) Pages: 139-146
  • URL: http://dx.doi.org/10.1016/j.antiviral.2012.02.013
  • Peer Reviewed
• [Journal Article] Editorial : Glycovirology (2012)
  • Author(s): Y. Suzuki
  • Journal Title: Open Glycoscience Volume: 5 Pages: 1
  • DOI: DOI:10.2174/1875398101205010001
  • Peer Reviewed
• [Journal Article] Bovine milk whey for preparation of natural N-glycans : structural and quantitative analysis (2012)
  • Author(s): N. Sriwilaijaroen, S. Kondo, H, Yagi, H. Hiramatsu, S. Nakakita, K. Yamada, H. Ito, J. Hirabayashi, H. Narimatsu, K. Kato and Y. Suzuki
  • Journal Title: Open Glycoscience Volume: 5 Pages: 41-50
  • DOI: doi:10.2174/1875398101205010041
  • Peer Reviewed
• [Journal Article] Experimental adaptation of an influenza H5 haemagglutinin confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets (2012)
  • Author(s): M. Imai, T. Watanabe, M. Hatta, S. C. Das, M. Ozawa, K. Shinya, G. Zhong, A. Hanson, H. Katsura, S. Watanabe, C. Li, E. Kawakami, S. Yamada, M. Kiso, Y. Suzuki, E. A. Maher, G. Neumann, Y. Kawaoka
  • Journal Title: Nature
  • DOI: doi:10.1038/nature10831
  • Peer Reviewed
• [Journal Article] Avian Influenza A virus(H5N1): the changing nature (2012)
  • Author(s): Y. Watanabe, M. S. Ibrahim, Y. Suzuki, K. Ikuta
  • Journal Title: Trends in Microbiology Volume: 20(1) Pages: 11-20
  • Peer Reviewed
• [Journal Article] Adaptation of a duck influenza A virus in quail (2012)
  • Author(s): S. Yamada, K. Shinya, A. Takada, T. Ito, T. Suzuki, Y. Suzuki, Q. Mai Le, M. Ebina, N. Kasai, H. Kida, T. Horimoto, Li Mei Chen, R. O. Donis, Y. Kawaoka
  • Journal Title: J. Virol Volume: 86(3) Pages: 1411-1420
  • Peer Reviewed
• [Journal Article] Highly pathogenic avian influenza (2011)
  • Author(s): Yasuo Suzuki
  • Journal Title: Journal of Disaster Research Volume: 6(4) Pages: 398-403
  • URL: http://www.fao.org/avianflu/en/index.html
  • Peer Reviewed
• [Journal Article] Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt (2011)
  • Author(s): Y. Watanabe, M. S. Ibrahim, H. F. Ellakany, N. Kawashita, R. Mizuike, H. Hiramatsu, N. Sriwilaijaroen, T. Takagi, Y. Suzuki and K. Ikuta
  • Journal Title: PLoS Pathogens Volume: 7 Pages: e-1002068
  • DOI: doi:10.1371/journal.ppat.1002068
  • Peer Reviewed
• [Journal Article] N-glycans from porcine trachea and lung : Predominant NeuAcα2-6Gal could be a selective pressure for influenza variants in favor of human-type receptor (2011)
  • Author(s): N. Sriwilaijaroen, S. Kondo, H. Yagi, N. T. T. Saito, H. Hiramatsu, K. Kato, Y. Suzuki
  • Journal Title: PLoS ONE Volume: 6 Pages: e-16302
  • DOI: doi:10.1371/journal.pone.0016302
  • Peer Reviewed
• [Journal Article] Mumefural and related HMF derivatives from Japanese apricot fruit juice concentrate show multiple inhibitory effects on pandemic influenza A(H1N1) virus (2011)
  • Author(s): N. Sriwilaijaroen, A. Kadowaki, Y. Onishi, N. Gato, M. Ujike, T. Odagiri, M. Tashiro, Y. Suzuki
  • Journal Title: Food Chem Volume: 127 Pages: 1-9
  • DOI: doi:10.1016/j.foodchem.2010.12.031
  • Peer Reviewed
• [Journal Article] Evaluation of a set of C9 N-acyl Neu5Ac2en mimetics as viral sialidase selective inhibitors (2011)
  • Author(s): S. Magesh, N. Sriwilaijaroen, M. Setsuko, H. Ando, M. Taeko, Y. Suzuki, H. Ishida and M. Kiso
  • Journal Title: International J. Medicinal Chemistry Volume: Vol.2011 Pages: 7
  • DOI: doi:10.1155/2011/539245(2010)
  • Peer Reviewed
• [Journal Article] The low-pH stability discovered in neuraminidase of 1918 pandemic influenza A virus enhances virus replication (2010)
  • Author(s): T. Takahashi, Y. Kurebayashi, K. Ikeya, T. Mizuno, K. Fukushima, H. Kawamoto, Y. Kawaoka, Y. Suzuki, T. Suzuki
  • Journal Title: PLoS ONE Volume: Vol.5 Pages: e-15556
  • DOI: doi:10.1371/journal.pone.0015556
  • Peer Reviewed
• [Journal Article] Influenza A(H5N1) viruses from pigs (2010)
  • Author(s): C. A. Nidom, R. Takano, S. Yamada, Y. S. Tagawa, S. Daulay, D. Aswadi, T. Suzuki, Y. Suzuki, K. I. Horimoto, K. Shinya, Y. Muramoto, Y. Kawaoka
  • Journal Title: Indonesia. Emerg. Infect. Dis Volume: 16 Pages: 1515-1523
  • DOI: doi:10.3201/eid1610.100508
  • Peer Reviewed
• [Journal Article] Emergence of H5N1 Avian Influenza Viruses with Reduced Sensitivity to Neuraminidase Inhibitors and Novel Reassortants in LAO PDR (2010)
  • Author(s): D. A. Boltz, B. Douangngeun, P. hommachanh, S. Sinthasak, R. Mondry, C. Obert, P. Seiler, R. Keating, Y. Suzuki, H. Hiramatsu, E. A. Govorkova, R. G. Webster
  • Journal Title: J. gen Virol Volume: 91 Pages: 949-959
  • DOI: doi:10.1099/vir.0.017459-0
  • Peer Reviewed
• [Journal Article] Alterations in receptor binding properties of swine influenza viruses of H1 subtype after isolation in embryonated chicken eggs (2010)
  • Author(s): N. Takemae, R. Ruttanapumma, S. Parchariyanon, S. Yoneyama, T. Hayashi, H. Hiramatsu, N. Sriwilaijaroen, Y. Uchida, S. Kondo, H. Yagi, K. Kato, Y. Suzuki, T. Saito
  • Journal Title: J. gen. Virol Volume: 91 Pages: 938-948
  • DOI: doi:10.1099/vir.0.016691-0
  • Peer Reviewed
• [Journal Article] Identification of amino acid residues of influenza A virus H3 HA containing to the recognition of molecular species of sialic acid (2009)
  • Author(s): T. Takahashi, A. Hashimoto, M. Murayama, H. Ishida, M. Kiso, Y. Kawaoka, Y. Suzuki, T. Suzuki
  • Journal Title: FEBS Lett Volume: 583(19) Pages: 3171-3174
  • DOI: doi:10.1016/j.febslet.2009.08.037
  • Peer Reviewed
• [Journal Article] Syntheses and biological evaluations of carbosilane dendrimers uniformly functionalized with sialyl α(2→3) lactose moieties as inhibitors for human influenza viruse (2009)
  • Author(s): T. Koyama, C.-T. Guo, Y. Suzuki, Y. Esumi, K. Hatano, D. Terunuma and K. Matsuoka
  • Journal Title: Bioorg. Med. Chem. Volume: 17 Pages: 5465-5475
  • DOI: doi:10.1016/j.bmc.2009.06.035
  • Peer Reviewed
• [Journal Article] Determination of N-linked sialyl-sugar chains in the lungs of domestic cats and dogs in Thailand susceptible to the highly pathogenic avian influenza virus(H5N1) (2009)
  • Author(s): Songserm, C. Poolkhet, S. Kondo, H. Yagi, H. Hiramatsu, M. Tashiro, H. Okada, K. Kato, Y. Suzuki
  • Journal Title: Open Glycoscience Volume: 2 Pages: 28-36
  • URL: http://creativecommons.org/licenses/by-nc/3.0/
  • Peer Reviewed
• [Journal Article] Analysis of N-glycans in embryonated chicken egg chorioallantoic and amniotic cells responsible for binding and adaptation of influenza viruses (2009)
  • Author(s): N. Sriwilaijaroen, S. Kondo, H. Yagi, P. Wilairat, H. Hiramatsu, M. Ito, Y. Ito, K. Kato, Y. Suzuki
  • Journal Title: Glycoconjugate J Volume: 26 Pages: 433-443
  • DOI: doi:10.1007/s10719-008-9193-x
  • Peer Reviewed
• [Journal Article] Limited inhibitory effects of Oseltamivir and Zanamivir on Human sialidases (2008)
  • Author(s): Hata, K. Koseki, K. Yamaguchi, S. Moriya, Y. Suzuki, S. Yingsakmongkon, Go Hirai, M. Sodeoka, M. von Itzstein, T. Miyagi
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 52 Pages: 3467-3471
  • DOI: doi:10.1128/AAC.00344-08
  • Peer Reviewed
• [Journal Article] Chemoenzymatic synthesis, characterization, and application of glycopolymers carrying lactosamie repeats as entry inhibitors against influenza virus infection (2008)
  • Author(s): IPJ Hidari, T. Murata, K. Yoshida, Y. Takahashi, Y. Minamijima, Y. Miwa, S. Adachi, M. Ogata, T. Usui, Y. Suzuki, T. Suzuki
  • Journal Title: Glycobiology Volume: 18 Pages: 779-788
  • DOI: doi:10.1093/glycob/cwn067
  • Peer Reviewed
• [Journal Article] Sulfatide regulates influenza A virus replication by association with hemagglutinin delivered to the cell surface (2008)
  • Author(s): Takahashi, K. Murakami, M. Nakagawa, H. Kishita, S. Watanabe, K. Honke, K. Ogura, T. Tai, K. Kawasaki, D. Miyamoto, K. I.-P. Jwa Hidari, C. T. Guo, Y. Suzuki, Takashi Suzuki
  • Journal Title: J. Virol Volume: 82(12) Pages: 5940-5950
  • DOI: doi:10.1128/JVI.02496-07
  • Peer Reviewed
• [Journal Article] In Vitro Inhibition of Human Influenza A Virus Infection by Fruit-Juice Concentrate of Japanese Plum(Prunus mume Sieb. et Zucc) (2008)
  • Author(s): Yingsakmongkon, D. Miyamoto, N. Sriwilaijaroen, K. Fujita, K. Matsumoto, W. Jampangern, H. Hiramatsu, C. T. Guo, T. Sawada, T. Tskahashi, K. Hidari, T. Suzuki, M. Ito, Y. Ito, Y. Suzuki
  • Journal Title: Biol. Pharm. Bull Volume: 31(3) Pages: 511-515
  • Peer Reviewed
• [Journal Article] Clarithromycin inhibits progeny virus production from influenza virus-Infected host cells (2008)
  • Author(s): Miyamoto, S. Hasegawa, N. Sriwilaijaroen, S. Yingsakmongkon, T. Suzuki, K. I.-P. J. Hidari, T. Takahashi, C.-T. Guo, Y. Sakano and Y. Suzuki
  • Journal Title: Biol. Pharm. Bull Volume: 31(2) Pages: 217-222
  • Peer Reviewed
• [Journal Article] A simple screening assay for receptor switching of avian influenza viruses (2008)
  • Author(s): Suptawiwat, A. Kongchanagul, W. Chan-It, A. Thitithanyanont, W. Wiriyarat, K. Chaichuen, T. Songserm, Y. Suzuki, P. Puthavathana, P. Auewarakul
  • Journal Title: J. Clinical Virol Volume: 42 Pages: 186-189
  • DOI: doi:10.1016/j.jcv.2008.01.014
  • Peer Reviewed
• [Journal Article] Mechanisms of the action of povidone-iodine against human and avian influenza A viruses : its effects on hemagglutination and sialidase activities
  • Author(s): Wilairat, H. Hiramatsu, T. Takahashi, T. Suzuki, M. Ito, Y. Ito, M. Tashiro, Y. Suzuki
  • Journal Title: Virology Journal Volume: 6 Pages: 124
  • DOI: doi:10.1186/1743-422X-6-124(2009)
  • Peer Reviewed
• [Presentation] Highly Pathogenic avian influenza-from bird to human-N-glycans from porcine trachea and lung : predominant Neu5Acα2-6Gal could be a selective pressure for influenza variants in favor of human-type receptor (2011)
  • Author(s): Yasuo Suzuki
  • Organizer: The 4^<th> Wuhan International Symposium on Modern Virology
  • Place of Presentation: Wuhan, China
  • Year and Date: 20111020-21
• [Book] How does the FMO method help in studying viruses and their binding to receptors (2009)
  • Author(s): T. Sawada, T. Hashimoto, H. Tokiwa, T. Suzuki, H. Nakano, H. Ishida, M. Kiso, and Y. Suzuki
  • Publisher: CRC press