The war against influenza: discovery and development of sialidase inhibitors

Abstract

The threat of a major human influenza pandemic, in particular from highly aggressive strains such as avian H5N1, has emphasized the need for therapeutic strategies to combat these pathogens. At present, two inhibitors of sialidase (also known as neuraminidase), a viral enzyme that has a key role in the life cycle of influenza viruses, would be the mainstay of pharmacological strategies in the event of such a pandemic. This article provides a historical perspective on the discovery and development of these drugs — zanamivir and oseltamivir — and highlights the value of structure-based drug design in this process.

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Figure 1: Influenza virus surface glycoproteins.
Figure 2: Life cycle of the influenza virus and targets for therapeutic intervention.
Figure 3: Chemical structures of selected compounds.
Figure 4: Interaction of α-N-acetylneuraminic acid (1a) with influenza virus sialidase.
Figure 5: Structures of influenza virus sialidase with zanamivir and oseltamivir carboxylate.

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Acknowledgements

The Australian Research Council is acknowledged for its generous support through the award of a Federation Fellowship. J. Dyason is thanked for providing a number of the computer-generated graphics and for reading this manuscript.

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DATABASES

Swissprot ENZYME

Exo-α-sialidase

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Griffith university institute of Glycomics

World Health organization

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von Itzstein, M. The war against influenza: discovery and development of sialidase inhibitors. Nat Rev Drug Discov 6, 967–974 (2007). https://doi.org/10.1038/nrd2400

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