Avishekh Gautam, David F Boyd, Sameer Nikhar, Ting Zhang, Ioannis Siokas, Lee-Ann Van de Velde, Jessica Gaevert, Victoria Meliopoulos, Bikash Thapa, Diego A Rodriguez, Kathy Q Cai, Chaoran Yin, Daniel Schnepf, Julius Beer, Carly DeAntoneo, Riley M Williams, Maria Shubina, Brandi Livingston, Dingqiang Zhang, Mark D Andrake, Seungheon Lee, Raghavender Boda, Anantha L Duddupudi, Jeremy Chase Crawford, Peter Vogel, Christian Loch, Martin Schwemmle, Lawrence C Fritz, Stacey Schultz-Cherry, Douglas R Green, Gregory D Cuny, Paul G Thomas, Alexei Degterev, Siddharth Balachandran
Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1-5 (ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6-8 and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo...
April 10, 2024: Nature