Antivirals active against henipaviruses will be an important component of a pandemic preparedness strategy. In the project “Small molecule drug development for henipaviruses” henipavirus antiviral compounds will be discovered by high throughput screening of small molecule compound libraries using a cell-based assay of cedar virus replication. Inhibitor compounds will be evaluated for broad spectrum activity across paramyxoviruses in cell-based assays. Medicinal chemistry optimization will be used to optimize inhibitor compounds to improve potency, selectivity, and drug-like properties. Orally active, broad spectrum antiviral inhibitors will be validated using infectious Nipah and Hendra viruses both in vitro and in vivo. Ultimately, the hope is that drugs can be stockpiled for use in future pandemics caused by henipaviruses. The 3-year project was initiated in late 2022 and is hosted by University of Illinois at Chicago, USA and the principal investigator is Lijun Rong.