MultiOMICs landscape of SARS-CoV2-induced host responses in human lung epithelial cells

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a global health pandemic. Despite the availability of vaccines and approved therapeutics, the emergence of newer plausible resistant variants continues to be on the rise. Several multi-omics studies have provided extensive evidence of host-pathogen interactions and potential therapeutic targets. However, an increased understanding of host cellular signaling networks regulated by multiple post-translational modifications and its ensuing effect on the biochemical and cellular dynamics is vital to expand the current knowledge on the host response to SARS-CoV-2 infections. Here, employing unbiased global proteomics, acetylomics, phosphoproteomics, RNA sequencing, and exometabolome analysis of a lung-derived human cell line, we show that SARS-CoV2 Norway/Trondheim-S15 strain induces time-dependent alterations in host cellular processes, including induction of type I IFN response, activation of DNA damage response pathway, RNA processing, metabolism, and cytoskeletal reorganization. We provide evidence for the interplay of phosphorylation and acetylation dynamics on host proteins and its effect on the altered release of metabolites, especially organic acids and ketone bodies. Together, our findings can serve as a resource for the identification of potential targets to design newer host-directed therapeutic strategies.