Proteomics in the COVID-19 Battlefield: First Semester Check-Up

Abstract

Proteomics offers a wide collection of methodologies to study biological systems at the finest granularity. Faced with COVID-19, the most worrying pandemic in a century, proteomics researchers have made significant progress in understanding how the causative virus hijacks the host's cellular machinery and multiplies exponentially, how the disease can be diagnosed, and how it develops, as well as its severity predicted. Numerous cellular targets of potential interest for the development of new antiviral drugs have been documented. Here, the most striking results obtained in the proteomics field over this first semester of the pandemic are presented. The molecular machinery of SARS-CoV-2 is much more complex than initially believed, as many post-translational modifications can occur, leading to a myriad of proteoforms and a broad heterogeneity of viral particles. The interplay of protein-protein interactions, protein abundances, and post-translational modifications has yet to be fully documented to provide a full picture of this intriguing but lethal biological threat. Proteomics has the potential to provide rapid detection of the SARS-CoV-2 virus by mass spectrometry proteotyping, and to further increase the knowledge of severe respiratory syndrome COVID-19 and its long-term health consequences.

Figure 1

SARS‐CoV‐2 machinery. Genomic organization and main characteristics of the SARS‐CoV‐2 structural proteins S, M, E, and N. A schematic overview of the protein domains and identified PTMs on N and S as described in Supekar et al., 2020 and Watanabe et al., 2020, respectively, is illustrated. N‐terminal domain, C‐terminal domain (CTD), RBD, fusion peptide (FP), heptad repeat 1 (HR1), central helix (CH), connector domain (CD), and transmembrane domain (TM).

Figure 2

Proteomics in the COVID‐19 battlefield. Examination of infected cell models and clinical samples by system‐wide unbiased discovery proteomics approaches is used to unravel the mechanisms employed by SARS‐CoV‐2 to bind, enter, hijack, and exit the host. Together with data from the SARS‐CoV‐2 profiling by mass spectrometry, these analyses provided a library of high‐quality viral peptide spectra that can be used for targeted proteomics detection. In addition, insights from the various multi‐level proteomics datasets represent a valuable resource for the identification of promising targets for therapeutic intervention. Besides, quantitative proteomics represents a promising tool to support the screening of drug repurposing libraries and for the understanding of cellular changes in metabolism occurring following initiation of anti‐SARS‐CoV‐2 treatment.

Figure 3

SARS‐CoV‐2‐host interactome. SARS‐CoV‐2‐Human PPIs commonly identified by both affinity purification (AP‐MS) and proximity‐dependent biotinylation (BioID) ‐based proteomics approaches. The network depicts PPIs described in^{[ 22} , ²⁷ , ³⁰ , ^{31 ]} and,^{[ 32} , ^{56 ]} respectively. The data are derived from BioGRID COVID‐19 Coronavirus Project.^{[ 57 ]} The subcellular localization of human proteins is labeled with the indicated colors. Viral proteins are represented by red hexagons. PPIs described only following one of the proteomics approaches^{[ 27} , ³¹ , ^{32 ]} are omitted.