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. 2021 Feb 5;20(2):1133-1152.
doi: 10.1021/acs.jproteome.0c00764. Epub 2021 Jan 19.

Proteomic Approaches to Study SARS-CoV-2 Biology and COVID-19 Pathology

Paige Haas  1   2   3   4 , Monita Muralidharan  1   2   3   4 , Nevan J Krogan  1   2   3   4   5 , Robyn M Kaake  1   2   3   4 , Ruth Hüttenhain  1   2   3   4
Affiliations

Proteomic Approaches to Study SARS-CoV-2 Biology and COVID-19 Pathology

Paige Haas et al. J Proteome Res. .

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was declared a pandemic infection in March 2020. As of December 2020, two COVID-19 vaccines have been authorized for emergency use by the U.S. Food and Drug Administration, but there are no effective drugs to treat COVID-19, and pandemic mitigation efforts like physical distancing have had acute social and economic consequences. In this perspective, we discuss how the proteomic research community can leverage technologies and expertise to address the pandemic by investigating four key areas of study in SARS-CoV-2 biology. Specifically, we discuss how (1) mass spectrometry-based structural techniques can overcome limitations and complement traditional structural approaches to inform the dynamic structure of SARS-CoV-2 proteins, complexes, and virions; (2) virus-host protein-protein interaction mapping can identify the cellular machinery required for SARS-CoV-2 replication; (3) global protein abundance and post-translational modification profiling can characterize signaling pathways that are rewired during infection; and (4) proteomic technologies can aid in biomarker identification, diagnostics, and drug development in order to monitor COVID-19 pathology and investigate treatment strategies. Systems-level high-throughput capabilities of proteomic technologies can yield important insights into SARS-CoV-2 biology that are urgently needed during the pandemic, and more broadly, can inform coronavirus virology and host biology.

Keywords: COVID-19; SARS-CoV-2; biomarker discovery; drug discovery; host response; mass spectrometry; protein−protein interactions; proteomics; structural proteomics; virus−host interactions.

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Figures

Figure 1.
Figure 1.
SARS-CoV-2 life cycle (A). Open questions to further our understanding of SARS-CoV-2 biology and proteomic techniques that can be leveraged to address these questions (B).
Figure 2.
Figure 2.
Overview of MS-based proteomics techniques proposed to study SARS-CoV-2, including sample types that can be used as input, molecular insights that can be obtained as output, and how the technologies can be integrated to inform SARS-CoV-2 biology and COVID-19 pathology.
See this image and copyright information in PMC

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