International Society for Antiviral Research

Targeting the multi-functional parainfluenza virus haemagglutinin-neuraminidase for drug discovery

Mark von Itzstein, PhD

Institute for Glycomics, Griffith University, Southport, Queensland, Australia

Human parainfluenza viruses (hPIV) are responsible for both upper and lower respiratory tract disease in children, the elderly and immunocompromised and hPIV infection can lead to a significant number of hospitalisations. Neither antiviral drugs nor vaccines are approved for clinical use against hPIV infection and consequently hPIV infection is an unmet clinical need that demands new therapeutic discovery strategies. We have had a longstanding interest in hPIV biology, particularly towards the discovery of novel inhibitors that could be advanced in a drug discovery program.

The viral surface glycoprotein haemagglutinin-neuraminidase (HN) plays a number of critical roles in the hPIV lifecycle and is a validated drug discovery target. We have used a multidisciplinary structure-guided approach to discover potent designer inhibitors that target a novel structural feature associated with the human parainfluenza virus type 3 (hPIV-3) HN protein. Our lead compounds have been identified and evaluated by several assays including  in vitro using enzymatic assays, in situ ELISA and an innovative infection assay utilising ex vivo differentiated human airway epithelium that mimic the natural human target tissue for respiratory viruses. 

Some of our advances in understanding the complexity of targeting the multifunctional HN protein will be presented, as well as aspects of our structure-guided anti-hPIV drug discovery program.

Lead References: V.P. Chibanga et al. Antiviral Res. 167:89-97 (2019); M. Pascolutti et al. ACS Chem. Biol. 13(6):1544-1550 (2018); L. Dirr et al. Sci. Rep. 7(1):4507. doi: 10.1038/s41598-017-04656-y (2017); P. Guillon et al. Nat. Commun. 5:5268 (2014).