Abstract
Infections by H1-H16 influenza A viruses require sufficient binding of viral hemagglutinins (HAs) to specific target receptors, glycoconjugates bearing sialyl sugar chains, on the host cell surface. Synthesized sialyl sugar chains targeting sialyl sugar-binding sites in HAs that are immutable as long as the virus does not switch to a different host species might therefore be highly effective candidate drugs for inhibition of the initial required step of virus entry. In this chapter, we describe the following aspects of updated sialyl sugar chains as influenza A virus HA inhibitors (HAIs): (1) mode of terminal sialyl-galactose linkage, (2) molecular length and structure of sialyl glycan receptors, (3) multivalent sialyl sugar chain dimension, (4) clustering of sialyl sugar chains on macromolecular scaffolds, and (5) enhancement of the stability of sialyl sugar chain HA inhibitors. We also discuss about the use of HAI-based combinations that should be considered for future influenza therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Change history
29 September 2020
The inadvertently published below contents have been corrected.
References
Sriwilaijaroen N, Suzuki Y (2012) Molecular basis of the structure and function of H1 hemagglutinin of influenza virus. Proc Jpn Acad Ser B Phys Biol Sci 88:226–249
McAuley JL, Gilbertson BP, Trifkovic S et al (2019) Influenza virus neuraminidase structure and functions. Front Microbiol 10(39):1–13
NIID website (2019) Antiviral resistance surveillance in Japan (as of 21 May 2019) https://www.niid.go.jp/niid/en/influ-resist-e.html
Sriwilaijaroen N, Magesh S, Imamura A et al (2016) A novel potent and highly specific inhibitor against influenza viral N1-N9 neuraminidases: insight into neuraminidase-inhibitor interactions. J Med Chem 59:4563–4577
Takashita E, Kawakami C, Morita H et al (2018) Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018. Euro Surveill 24(3):1–5
Guo H, Rabouw H, Slomp A et al (2018) Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces. PLoS Pathog 14:e1007233
Suzuki Y (2005) Sialobiology of influenza-molecular mechanism of host range variation of influenza viruses. Biol Pharm Bull 28:399–408
Stevens J, Blixt O, Paulson JC et al (2006) Glycan microarray technologies: tools to survey host specificity of influenza viruses. Nat Rev Microbiol 4:857–864
Sriwilaijaroen N, Kondo S, Yagi H et al (2009) Analysis of N-glycans in embryonated chicken egg chorioallantoic and amniotic cells responsible for binding and adaptation of human and avian influenza viruses. Glycoconj J 26:433–443
Watanabe Y, Ito T, Ibrahim MS et al (2015) A novel immunochromatographic system for easy-to-use detection of group 1 avian influenza viruses with acquired human-type receptor binding specificity. Biosens Bioelectron 65:211–219
Matrosovich M, Herrler G, Klenk HD (2015) Sialic acid receptors of viruses. Top Curr Chem 367:1–28
Shi J, Deng G, Kong H et al (2017) H7N9 virulent mutations detected in chicken in China pose an increased threat to humans. Cell Res 12:1409–1421
de Vries RP, Peng W, Grant OC et al (2017) Three mutations switch H7N9 influenza to human-type receptor specificity. PLoS Pathog 13:e1006390
Imai M, Watanabe T, Hatta M et al (2012) Experimental adaptation of an influenza H5 haemagglutinin confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486:420–428
Ng PS, Böhm R, Hartley-Tassell LE et al (2014) Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors. Nat Commun 5:5750
Velkov T (2013) The specificity of the influenza B virus hemagglutinin receptor binding pocket: what does it bind to? J Mol Recognit 26:439–449
Sriwilaijaroen N, Suzuki Y (2014) Molecular basis of a pandemic of avian-type influenza virus. Methods Mol Biol 1200:447–480
Walther T, Karamanska R, Chan RW et al (2013) Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog 9:e1003223
Sriwilaijaroen N, Nakakita S, Kondo S et al (2018) N-Glycan structures of human alveoli provide insight into influenza A virus infection and pathogenesis. FEBS J 285:1611–1634
Peng W, de Vries RP, Grant OC et al (2017) Recent H3N2 viruses have evolved specificity for extended, branched human-type receptors, conferring potential for increased avidity. Cell Host Microbe 21:23–34
Hidari KI, Murata T, Yoshida K et al (2008) Chemoenzymatic synthesis, characterization, and application of glycopolymers carrying lactosamine repeats as entry inhibitors against influenza virus infection. Glycobiology 18:779–788
Weis W, Brown JH, Cusack S et al (1988) Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature 333:426–431
Ohta T, Miura N, Fujitani N et al (2003) Glycotentacles: synthesis of cyclic glycopeptides, toward a tailored blocker of influenza virus hemagglutinin. Angew Chem Int Ed Engl 42:5186–5189
Yamabe M, Kaihatsu K, Ebara Y (2018) Sialyllactose-modified three-way junction DNA as binding inhibitor of influenza virus hemagglutinin. Bioconjug Chem 29:1490–1494
Hanson JE, Sauter NK, Skehel JJ et al (1992) Proton nuclear magnetic resonance studies of the binding of sialosides to intact influenza virus. Virology 189:525–533
Tsuchida A, Kobayashi K, Matsubara N et al (1998) Simple synthesis of sialyllactose-carrying polystyrene and its binding with influenza virus. Glycoconj J 15:1047–1054
Totani K, Kubota T, Kuroda T et al (2003) Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyloligosaccharides with a poly (L-glutamic acid) backbone for inhibition of infection by influenza viruses. Glycobiology 13:315–326
Ogata M, Murata T, Murakami K et al (2007) Chemoenzymatic synthesis of artificial glycopolypeptides containing multivalent sialyloligosaccharides with a gamma-polyglutamic acid backbone and their effect on inhibition of infection by influenza viruses. Bioorg Med Chem 15:1383–1393
Makimura Y, Watanabe S, Suzuki T et al (2006) Chemoenzymatic synthesis and application of a sialoglycopolymer with a chitosan backbone as a potent inhibitor of human influenza virus hemagglutination. Carbohydr Res 341:1803–1808
Guo CT, Sun XL, Kanie O et al (2002) An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses. Glycobiology 12:183–190
Guo CT, Wong CH, Kajimoto T et al (2002) Synthetic sialylphosphatidylethanolamine derivatives bind to human influenza A viruses and inhibit viral infection. Glycoconj J 15:1099–1108
Sun XL, Kanie Y, Guo CT et al (2000) Synthesis of C-3 modified sialylglycosides as selective inhibitors of influenza hemagglutinin and neuraminidase. Eur J Org Chem 2000:2643–2653
Oka H, Onaga T, Koyama T et al (2009) Syntheses and biological evaluations of carbosilane dendrimers uniformly functionalized with sialyl α(2-3) lactose moieties as inhibitors for human influenza viruses. Bioorg Med Chem 17:5465–5475
Kamitakahara H, Suzuki T, Nishigori N et al (1998) A lysoganglioside/poly-L-glutamic acid conjugate as a picomolar inhibitor of influenza hemagglutinin. Angew Chem Int Ed Engl 37:1524–1528
Sriwilaijaroen N, Suzuki Y (2014) A simple viral neuraminidase-based detection for high-throughput screening of viral hemagglutinin-host receptor specificity. Methods Mol Biol 1200:107–120
Yang Y, Liu HP, Yu Q et al (2016) Multivalent S-sialoside protein conjugates block influenza hemagglutinin and neuraminidase. Carbohydr Res 435:68–75
WHO website (2010) WHO guidelines for pharmacological management of pandemic influenza A(H1N1) 2009 and other influenza viruses. https://www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf
CDC website (2018) Influenza antiviral medications: summary for clinicians. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
Sriwilaijaroen N, Suzuki K, Takashita E et al (2015) 6SLN-lipo PGA specifically catches (coats) human influenza virus and synergizes neuraminidase-targeting drugs for human influenza therapeutic potential. J Antimicrob Chemother 70:2797–2809
Lin Q, Li T, Chen Y et al (2018) Structural basis for the broad, antibody-mediated neutralization of H5N1 influenza virus. J Virol 92(17):e00547–e00518
Ekiert DC, Friesen RH, Bhabha G et al (2011) A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 333:843–850
van Dongen MJP, Kadam RU, Juraszek J et al (2019) A small-molecule fusion inhibitor of influenza virus is orally active in mice. Science 363(6431):eaar6221
Chen Q, Guo Y (2016) Influenza viral hemagglutinin peptide inhibits influenza viral entry by shielding the host receptor. ACS Infect Dis 2:187–193
Lauster D, Glanz M, Bardua M et al (2017) A multivalent peptide-nanoparticle conjugates for influenza-virus inhibition. Angew Chem Int Ed Engl 56:5931–5936
Zeng LY, Yang J, Liu S (2017) Investigational hemagglutinin-targeted influenza virus inhibitors. Expert Opin Investig Drugs 26:63–73
Sriwilaijaroen N, Kadowaki A, Onishi Y et al (2011) Mumefural and related HMF derivatives from Japanese apricot fruit juice concentrate show multiple effects on pandemic influenza A (H1N1) virus. Food Chem 127:1–9
Sriwilaijaroen N, Fukumoto S, Kumagai K et al (2012) Antiviral effects of Psidium guajava Linn. (guava) tea on the growth of clinical isolated H1N1 viruses: its role in viral hemagglutination and neuraminidase inhibition. Antivir Res 94:139–146
Kido H, Okumura Y, Takahashi E et al (2009) Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses. J Mol Genet Med 3:167–175
Wua CY, Lina CW, Tsaia TI et al (2017) Influenza a surface glycosylation and vaccine design. Proc Natl Acad Sci U S A 114:280–285
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Sriwilaijaroen, N., Suzuki, Y. (2020). Hemagglutinin Inhibitors are Potential Future Anti-Influenza Drugs for Mono- and Combination Therapies. In: Hirabayashi, J. (eds) Lectin Purification and Analysis. Methods in Molecular Biology, vol 2132. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0430-4_48
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0430-4_48
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0429-8
Online ISBN: 978-1-0716-0430-4
eBook Packages: Springer Protocols