<p>Primers used for RT-qPCR.</p>

Here we identify GSDMA as an immunomodulatory protein activated in response to coronavirus (CoV) infection. Specifically, CoV-encoded protease nsp5 cleaves GSDMA at two conserved glutamine sites, Q247 and Q187.

Cleavage at Q247 liberates an active N-terminal fragment (GSDMA_1–247) that triggers pyroptosis, promotes inflammation, and restricts viral replication. In contrast, cleavage at the alternative site Q187 attenuates this function. Using <i>Gsdma</i>^-/- mice, we show that GSDMA deficiency increases viral loads but reduces inflammation, tissue damage, and mortality upon infection.