The Development of Carbohydrate-Based Influenza Virus Sialidase Inhibitors

  • Robin Thomson
  • Mark von Itzstein
Part of the Milestones in Drug Therapy book series (MDT)


This chapter presents a review of the development of influenza virus sialidase inhibitors based on a carbohydrate scaffold, predominantly that of the natural ‘ligand’ of the enzyme, N-acetylneuraminic acid (Neu5Ac). These inhibitors include hydrolytically stable substrate-like compounds, product mimics, and transition-state-like compounds. The major focus of the chapter, reflecting the most intensively researched area of inhibitor development, is on the use of the dihydropyran scaffold of the 2,3-unsaturated-Neu5Ac derivative, Neu5Ac2en, a putative transition state mimic. Structure-based drug design targeting conserved residues of the sialidase active site using this template leading to the development of the potent and selective inhibitor, and anti-influenza drug, zanamivir (Relenza™), as well as subsequent developments towards next generation inhibitors, are discussed.


Influenza Virus Sialic Acid Influenza Virus Infection Oseltamivir Carboxylate Guanidino Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Neuraminidase (sialidase)


N-acetylneuraminic acid


2-deoxy-2,3-didehydro-N-acetylneuraminic acid


Madin-Darby canine kidney (cell line)



The financial support of the Australian Research Council (ARC) through the award of an Australian Federation Fellowship (MvI), the National Health and Medical Research Council (NHMRC), and the Honda Foundation (Australia) is gratefully acknowledged.


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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  1. 1.Institute for GlycomicsGriffith UniversitySouthportAustralia

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