Dynamic Cellular\nProteome Remodeling during SARS-CoV‑2\nInfection. Identification of Plasma Protein Readouts

The outbreak of COVID-19, led to an ongoing pandemic\nwith devastating\nconsequences for the global economy and human health. With the global\nspread of SARS-CoV-2, multidisciplinary initiatives were launched\nto explore new diagnostic, therapeutic, and vaccination strategies.\nFrom this perspective, proteomics could help to understand the mechanisms\nassociated with SARS-CoV-2 infection and to identify new therapeutic\noptions. A TMT-based quantitative proteomics and phosphoproteomics\nanalysis was performed to study the proteome remodeling of human lung\nalveolar cells expressing human ACE2 (A549-ACE2) after infection with\nSARS-CoV-2. Detectability and the prognostic value of selected proteins\nwas analyzed by targeted PRM. A total of 6802 proteins and 6428 phospho-sites\nwere identified in A549-ACE2 cells after infection with SARS-CoV-2.\nThe differential proteins here identified revealed that A549-ACE2\ncells undergo a time-dependent regulation of essential processes,\ndelineating the precise intervention of the cellular machinery by\nthe viral proteins. From this mechanistic background and by applying\nmachine learning modeling, 29 differential proteins were selected\nand detected in the serum of COVID-19 patients, 14 of which showed\npromising prognostic capacity. Targeting these proteins and the protein\nkinases responsible for the reported phosphorylation changes may provide\nefficient alternative strategies for the clinical management of COVID-19.