Fig. 5.

Treatment with p38 inhibitors PH and VX maintains the antiviral type I IFN response in SARS-CoV-2 infected human lung epithelial (AT-II) organoids. Human lung stem cell organoids from three patients were treated with DMSO (control) or the inhibitors PH and VX (5 μM) after infection with SARS-CoV-2 (MOI 1). A) SARS-CoV-2-induced immune response in non-treated cells (non-infected/infected) and inhibitor-treated infected cells (non-infected/PH-797804, non-infected/VX-702) from human lung stem cell organoids. Volcano plots displaying gene expression from RNAseq analysis; adj. p-value <0.05, <1.5-fold change (Log₂ = 0.5849625). B) Replication of SARS-CoV-2 in the human lung epithelial organoids treated or non-treated with PH and VX (5 μM). C) Top 10 biological processes induced by SARS-CoV-2 infection with or without p38 inhibition. Analysis was performed using GO term enrichment for all up-regulated DEGs comparing infected control and infected treated cells with PH or VX (5 μM). D) Gene expression levels of COVID-19 relevant antiviral restriction factors. Data are displayed as n-fold induction over non-treated and non-infected organoids. Bars represent mean values ± SEM from three donors. Statistical significance was determined using one-way ANOVA followed by Dunnett's multiple comparison test. *p < 0.05; **p < 0.01, ***p < 0.001.