Highlights•Targeting Hsp90 significantly reduced PEDV, PDCoV, TGEV or SADS-CoV infection in porcine cells or intestinal organoids.•The N proteins of PEDV, PDCoV, TGEV or SADS-CoV are the clients of porcine Hsp90.•Human Hsp90 interacts with the SADS-CoV N protein and prevents its autophagic degradation.•SADS-CoV can trigger human caspase-1/GSDMD-mediated pyroptotic cell death.