Towards a pan-viral map of motif-based host-virus interactions and its application for antiviral development.

We will take a systems biology approach to map end exploit Short Linear Motif (SLiM)-based host-virus protein-protein interactions.

SLiMs are 3-10 amino acid stretches that serve as compact binding sites, which give rise to interactions that are crucial for cell signaling.

Viral proteins mimic human SLiMs to take over the host cell machinery and these interactions have crucial roles in viral infections.

We have developed a unique platform for large-scale screening of SLiM-based interactions, including phage libraries displaying peptides from over 300 viral species.

We will screen for interactions among a large collection of human bait proteins, including E3 ligases, deubiquitinases and kinases, which will provide large-scale pan-viral data on SLiM-based viral hijacking. The results will be integrated through systematic network analysis.

We will identify host proteins and processes serving as common hubs of viral interference, and validate key interactions through biophysical and virological assays.

We will further screen for peptides with antiviral activities and optimize lead peptides, and establish their mechanism of action. The data will be made available to the community through a dedicated web portal.

Our findings will provide novel insights into the interactions underlying viral infection and open novel avenues for antiviral development.