SARS-CoV-2 Activates the p38/MAPK Signaling Pathway and Causes Cell Cycle Arrest (A) Diagram of the p38/MAPK signaling pathway. (B) Kinase activity analysis for kinases in the p38/MAPK pathway. (C) Western blot analysis of phosphorylated p38/MAPK signaling components in mock- and SARS-CoV-2-infected ACE2-A549 cells 24 h after infection. (D) Log2 fold change profiles of indicated p38/MAPK substrates during SARS-CoV-2 infection in Vero E6 cells. (E) Transcription factor activity analysis of SARS-CoV-2-infected A549, Calu-3, and NHBE cells, comparing p38/MAPK transcription factors with transcription factors not associated with the p38/MAPK pathway. Statistical test: Mann-Whitney test. (F) qRT-PCR analysis of the indicated mRNA from ACE2-A549 cells pre-treated with the p38 inhibitor SB203580 at the indicated concentrations for 1 h prior to infection with SARS-CoV-2 for 24 h. Statistical test: Student’s t test. See also Figures S4 and S5. (G) Heatmap of Pearson’s correlation coefficients comparing SARS-CoV-2-infected Vero E6 phosphorylation profiles with profiles of cells with induced DNA damage and cells arrested at the indicated cell cycle stages. (H) Log2 fold change profiles of the indicated cell cycle and DNA damage substrates during SARS-CoV-2 infection in Vero E6 cells. (I) DNA content analysis of cells infected with SARS-CoV-2 for 24 h compared with mock-infected cells.