Project C05.2

Lassa virus (LASV), a causative agent of severe hemorrhagic fever, is listed on the WHO Research and Development Blueprint of epidemic threats, underlining the importance of developing medical countermeasures [1]. Protein-protein interactions (PPI) during the viral life cycle exhibit potential targets for intervention. A promising example is the interaction between the viral matrix protein Z and the polymerase L, where Z has an inhibiting function on polymerase activity and presumably induces a switch from viral replication towards assembly and egress of particles [2]. The interactions of Z with the LASV glycoprotein and host factors for intracellular protein transport and packaging of viral particles display further important PPI to target [3]. New methods in structure-based drug discovery enable de-novodesign of protein inhibitors to interfere with those crucial PPI and lead to a disruption in the viral life cycle [4,5]. 

In this project, we aim to design such inhibitors using computational tools including machine-learning models. Further, computer simulations as well as wet-lab experiments using for example bio-layer interferometry, bioluminescence resonance energy transfer and cryo EM will allow us to validate the effect and mechanism of the designed inhibitors. Our goal is to evaluate their potential as antiviral strategies or analytical tools to deepen our molecular understanding of LASV infection.