Proteolysis targeting chimeras (PROTACs) a new strategy to develop broad-spectrum antiviral agents

New antiviral agents are urgently needed for preparedness towards future influenza virus (IV) pandemics and for combatting critical infections caused by IVs and human parainfluenza viruses (hPIVs), for which no drugs are currently available.

The emergence of resistance towards approved IV drugs makes it necessary to consider development of drugs with new modes of action. This proposal aim to apply the PROTAC technology to develop broad-spectrum antivirals targeting IV/hPIV. PROTACs act by inducing degradation of target proteins in contrast to inhibition of protein function.

The first part of this 3-year project will be performed in Prof. von Itzstein’s research group at Griffith University.

They have discovered a potent broad-spectrum inhibitor of IV neuraminidase (NA) and hPIV hemagglutinin-neuraminidase (HN) that I will incorporate into a PROTAC molecule. They have also discovered new starting points for hit–to–lead development.

The goal of this proposal is to design, synthesize and evaluate potent and selective NA/HN ligands and to incorporate them into PROTAC molecules. Year 3 will be performed at Uppsala University (UU) with Prof. Anders Karlén and Assoc. Prof. Moodie as hosts.

Their combined experience in anti-infective research will be of great importance to further establish the PROTAC technology in this research area.

The research environment at GU/UU is ideal for this project including expertise, technical capabilities, and infrastructural resources.