Mass spectrometry-based proteomic platforms for better understanding of SARS-CoV-2 induced pathogenesis and potential diagnostic approaches

Proteomics. 2021 May;21(10):e2000279. doi: 10.1002/pmic.202000279. Epub 2021 May 5.


While protein-protein interaction is the first step of the SARS-CoV-2 infection, recent comparative proteomic profiling enabled the identification of over 11,000 protein dynamics, thus providing a comprehensive reflection of the molecular mechanisms underlying the cellular system in response to viral infection. Here we summarize and rationalize the results obtained by various mass spectrometry (MS)-based proteomic approaches applied to the functional characterization of proteins and pathways associated with SARS-CoV-2-mediated infections in humans. Comparative analysis of cell-lines versus tissue samples indicates that our knowledge in proteome profile alternation in response to SARS-CoV-2 infection is still incomplete and the tissue-specific response to SARS-CoV-2 infection can probably not be recapitulated efficiently by in vitro experiments. However, regardless of the viral infection period, sample types, and experimental strategies, a thorough cross-comparison of the recently published proteome, phosphoproteome, and interactome datasets led to the identification of a common set of proteins and kinases associated with PI3K-Akt, EGFR, MAPK, Rap1, and AMPK signaling pathways. Ephrin receptor A2 (EPHA2) was identified by 11 studies including all proteomic platforms, suggesting it as a potential future target for SARS-CoV-2 infection mechanisms and the development of new therapeutic strategies. We further discuss the potentials of future proteomics strategies for identifying prognostic SARS-CoV-2 responsive age-, gender-dependent, tissue-specific protein targets.

Keywords: COVID-19; biomarkers; comparative proteomics; kinase-substrate signaling; post-translational modifications; targeted proteomics; top-down proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • COVID-19 / diagnosis
  • COVID-19 / metabolism*
  • COVID-19 / pathology
  • Host-Pathogen Interactions*
  • Humans
  • Mass Spectrometry / methods*
  • Protein Interaction Mapping / methods
  • Protein Interaction Maps
  • Protein Kinases / analysis
  • Protein Kinases / metabolism
  • Protein Processing, Post-Translational
  • Proteome / analysis
  • Proteome / metabolism
  • Proteomics / methods*
  • Receptor, EphA2 / analysis
  • Receptor, EphA2 / metabolism
  • SARS-CoV-2 / physiology*
  • Signal Transduction


  • Proteome
  • Protein Kinases
  • Receptor, EphA2