Updated project metadata. To identify the proteome alterations in human epithelial cells upon SARS-CoV-2 infection, we performed an in vitro experiment, where we infected lung-adenocarcinoma cultured human airway epithelial cells (Calu-3) with an isolate of the ancestral variant and alpha variant of SARS-CoV-2 in two separate experiments. Samples were then collected 3 hours, 1 day, 3 days, and 7 days post infection. In parallel, for comparison, we collected samples on the same days from non-infected cells and cells treated with SARS-CoV-2 virus (of the corresponding variant) inactivated by ultraviolet radiation. All conditions were performed in biological triplicates and we performed proteomics analysis with high-pH fractionation and LC-MS/MS.