Dynamic Cellular Proteome Remodeling during SARS-CoV‑2 Infection. Identification of Plasma Protein Readouts

The outbreak of COVID-19, led to an ongoing pandemic
with devastating
consequences for the global economy and human health. With the global
spread of SARS-CoV-2, multidisciplinary initiatives were launched
to explore new diagnostic, therapeutic, and vaccination strategies.
From this perspective, proteomics could help to understand the mechanisms
associated with SARS-CoV-2 infection and to identify new therapeutic
options. A TMT-based quantitative proteomics and phosphoproteomics
analysis was performed to study the proteome remodeling of human lung
alveolar cells expressing human ACE2 (A549-ACE2) after infection with
SARS-CoV-2. Detectability and the prognostic value of selected proteins
was analyzed by targeted PRM. A total of 6802 proteins and 6428 phospho-sites
were identified in A549-ACE2 cells after infection with SARS-CoV-2.
The differential proteins here identified revealed that A549-ACE2
cells undergo a time-dependent regulation of essential processes,
delineating the precise intervention of the cellular machinery by
the viral proteins. From this mechanistic background and by applying
machine learning modeling, 29 differential proteins were selected
and detected in the serum of COVID-19 patients, 14 of which showed
promising prognostic capacity. Targeting these proteins and the protein
kinases responsible for the reported phosphorylation changes may provide
efficient alternative strategies for the clinical management of COVID-19.