@article{5806,
  keywords = {Cell death and immune response, Influenza virus},
  author = {Avishekh Gautam and David F. Boyd and Sameer Nikhar and Ting Zhang and Ioannis Siokas and Lee-Ann Van de Velde and Jessica Gaevert and Victoria Meliopoulos and Bikash Thapa and Diego A. Rodriguez and Kathy Q. Cai and Chaoran Yin and Daniel Schnepf and Julius Beer and Carly DeAntoneo and Riley M. Williams and Maria Shubina and Brandi Livingston and Dingqiang Zhang and Mark D. Andrake and Seungheon Lee and Raghavender Boda and Anantha L. Duddupudi and Jeremy Chase Crawford and Peter Vogel and Christian Loch and Martin Schwemmle and Lawrence C. Fritz and Stacey Schultz-Cherry and Douglas R. Green and Gregory D. Cuny and Paul G. Thomas and Alexei Degterev and Siddharth Balachandran},
  title = {Necroptosis blockade prevents lung injury in severe influenza},
  abstract = {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. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesting that RIPK3 blockade may provide clinical benefit in patients with IAV-driven ARDS and other hyper-inflammatory pathologies.},
  year = {2024},
  journal = {Nature},
  volume = {628},
  pages = {835-843},
  month = {2024-04},
  issn = {1476-4687},
  url = {https://www.nature.com/articles/s41586-024-07265-8},
  doi = {10.1038/s41586-024-07265-8},
  language = {en},
}