Necroptosis is a targetable driver of severe coronavirus pathogenesis

Highly pathogenic human coronaviruses trigger necroptosis in infected cells and lung tissues, unlike seasonal coronaviruses, with Z-RNA–ZBP1 signaling linked to necroinflammation and lung injury.

• Why it matters: The mechanisms behind why some coronaviruses cause severe disease are incompletely understood, limiting targeted therapies for lung inflammation and injury.
• What they did: The study compared infected cells and lung tissues from highly pathogenic versus seasonal coronaviruses, testing whether Z-RNA activates ZBP1 to initiate necroptosis, and then used small-molecule necroptosis inhibition in mice infected with all three highly pathogenic coronaviruses.
• The result: Necroptosis blockade reduced inflammatory cytokine expression and markedly ameliorated lung damage in mice, independent of virus clearance, supporting necroptosis as a dominant mediator and therapeutic target.

AI summary of the abstract · may contain errors · not medical advice · read the paper.