Ultrasound‐microbubble‐mediated kidney‐specifically overexpressing SARS‐CoV‐2 N protein induces AKI in normal mice, which becomes worse in mice with ischemic reperfusion injury (IRI). A–C) SARS‐CoV‐2 N induces AKI in normal mice. D–F) SARS‐CoV‐2 N causes severe AKI in IRI‐mice. A,D) PAS staining. B,E) Semiquantitative analysis of tubular necrosis. C,F) Serum levels of creatinine. Note that kidney‐specifically SARS‐CoV‐2 N‐expressing plasmid transfer (200 µg/per mice) causes moderate AKI in normal mice by significantly increasing tubular necrosis (*) and serum levels of creatinine, which becomes worse in IRI‐mice. Each dot represents one mouse and data are expressed as the mean ± SEM for groups of six mice. *p < 0.05, ***p < 0.001 versus sham or normal control group; #p < 0.05, ###p < 0.001 versus empty vector control (VC) group. g, glomerulus; scale bars = 50 µm.