Fig. 6.

ALK1 inhibitor suppresses SARS-CoV-2-induced endothelial hyperpermeability and mortality in mice. (A) Schematic illustration of the airway-on-a-chip. Medium containing 0.1 MOI SARS-CoV-2 was injected into the airway channel. The SARS-CoV-2-infected airway-on-a-chips were cultured with the AO differentiation medium (airway channel) and DMSO- or K02288 (1 µM)-containing EGM2-MV medium (vascular channel) for 6 d. (B) Viral copy numbers in the cell culture supernatant of the airway and vascular channels (*P < 0.05 by the unpaired t test). (C) Immunofluorescent staining for VE-cadherin in the lung microvascular ECs in the airway-on-a-chip. (D) Robo4 expression levels in lungs of SARS-CoV-2 infected BALB/c mice treated with or without K02288 (n = 5, *P < 0.05 by the unpaired t test). (E) Survival study of SARS-CoV-2-infected BALB/c mice treated with or without K02288 (control: n = 10, K02288: n = 10; P = 0.025 by the log-rank test). We defined the day that mice had less than 75% of the initial body weight as the day of death. (F) Representative images of hematoxylin and eosin-stained lung sections from SARS-CoV-2-infected mice with or without K02288 treatment and noninfected mice. Data are expressed as the mean ± SEM.