Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Targeting respiratory viruses using structure-guided inhibitor design on glycoenzymes (#60)

Mark von Itzstein 1
  1. Griffith University, Southport, QLD, Australia

Viruses have a long history of causing significant disease throughout the centuries.  Immense impact on world socioeconomics has occurred as a consequence of virus-caused diseases, for example Hong Kong’s borders were closed as a result of the appearance of the SARS coronavirus and shut down trade and all travel within this region.

Viruses transmitted in aerosolised particles from human to human by coughing and sneezing, such as influenza virus, remain of utmost concern given the potential of rapid pandemic waves due to international travel.

Influenza virus continues to cause both epidemics and pandemics. Successful inhibition of the viral sialidase (neuraminidase, NA) hinders the release of new virus progeny from an infected host cell and significantly reduces further virus spread. We have recently described the discovery of highly potent sialosyl sulfonate inhibitors of influenza virus sialidase.1,2 One of the designer sialosyl a-sulfonate derivatives is a nanomolar inhibitor2 in a cell-based influenza virus replication assay and has comparable activity to that of anti-influenza drugs zanamivir and oseltamivir carboxylate. Furthermore, we have undertaken a protein X-ray crystallographic study that provides atomic-level detail of the binding mode of these sialosyl a-sulfonate derivatives.2


  1. Á. Hadházi, M. Pascolutti, B. Bailly, J. C. Dyason, A. Borbás, R. J. Thomson, M. von Itzstein, Biomol. Chem. 2017, 15, 5249-5253.
  2. Á. Hadházi, L. Li, B. Bailly, A. Maggioni, G. Martin, L. Dirr, J. C. Dyason, R. J. Thomson, G. F. Gao, A. Borbás, T. Ve, M. Pascolutti, M. von Itzstein, ChemMedChem. 2018, 13, 785-789.