Antivirals active against viruses belonging to the henipavirus subfamily of paramyxoviruses will be an important component of pandemic preparedness. In the project ‘Discovery of directly-acting small molecule inhibitors of henipaviruses’ high throughput screening of small molecule compound libraries will be used to identify inhibitors of henipavirus infection using a cell-based assay of cedar virus replication as a surrogate for highly pathogenic human henipaviruses. Inhibitors will be optimized through medicinal chemistry to improve potency, selectivity, and drug-like properties. Active compounds will be evaluated for antiviral activity against authentic human henipaviruses in BSL-4 containment and also other viruses to determine selectivity. An animal model of cedar virus replication will be developed to characterize promising hit compounds for antiviral activity in vivo. The 3-year project is hosted at KU Leuven in Belgium, headed by Professor Johan Neyts and started in November 2022.
Picture above, provided by KU Leuven, is a co-culture of VeroE6 cells stably expressing mCherry (red) in the nucleus and either GFP1-10 or GFP11 in the cytoplasm (GFP split). Infection with the Cedar virus results in cell-cell fusion and therefore the formation of GFP-positive syncytia (green), which allows for monitoring of infection in real-time, without the need for a reporter.