To gain new biological insights - Virus research solutions

Significance of the Topic

Rapid characterization of viral pathogens and their interactions with host cells is critical for guiding public health responses, informing vaccine design, and accelerating therapeutic development. Omics approaches anchored by high-resolution mass spectrometry deliver comprehensive molecular profiles that reveal virus structure, protein modifications, and metabolic perturbations in infected cells. By leveraging advanced workflows in proteomics, glycomics, lipidomics, and metabolomics, researchers can decode viral mechanisms, identify biomarkers, and develop sensitive detection assays that address urgent needs in global virus surveillance and clinical diagnostics.

Objectives and Study Overview

This study outlines a suite of mass spectrometry–based solutions for virus research developed by Thermo Fisher Scientific. It surveys workflows for quantitative and discovery proteomics, analysis of post-translational modifications, integrative structural biology, targeted viral protein detection, and metabolomics of infected biological systems. The goals include mapping viral proteomes, elucidating glycosylation and phosphorylation patterns, characterizing viral particle architecture, creating high-throughput assays for pathogen detection, and uncovering host metabolic signatures associated with infection.

Methodology and Instrumentation

A broad portfolio of instrumentation and reagents supports the described workflows:

• Orbitrap-based mass spectrometers (Exploris 480, Eclipse Tribrid, ID-X Tribrid, Q Exactive UHMR) for high-resolution accurate-mass analysis across proteomics and structural studies
• Vanquish Neo and Horizon UHPLC systems with EASY-Spray PepMap Neo and Accucore RP columns for robust chromatographic separation
• Sample preparation kits including EasyPep MS, HyperSep Retain AX cartridges, High-Select Fe-NTA phosphopeptide enrichment, and Pierce peptide standards for quality control
• Targeted quantitation technologies such as TSQ Altis triple quadrupole for SRM, Orbitrap PRM, and SureQuant internal standard workflows for sensitive viral protein detection
• Specialized modules for integrative structural biology including LEAP HDX systems, FAIMS Pro interface, crosslinking reagents (DSSO, DSBU), and SEC columns for native mass spectrometry
• Software platforms such as Proteome Discoverer with nodes for Byonic, ptmRS, XlinkX, ProSightPD; Skyline and TraceFinder for targeted analysis; Compound Discoverer, mzCloud, and BioPharma Finder for metabolomics and structural data interpretation

Main Results and Discussion

Quantitative proteomics workflows (LFQ, TMT) enable precise measurement of viral epitopes and host response proteins across infection time courses. Glycoproteomics and glycomics reveal site-specific glycan compositions on viral envelope proteins critical for immune evasion and binding. Phosphoproteome mapping uncovers dynamic host signaling modifications triggered by viral entry. Integrative structural approaches including native MS, HDX-MS, crosslinking, and top-down analysis provide atomic-level insights into capsid assembly, protein–protein interactions, and proteoform diversity. Targeted SRM, PRM, and SureQuant assays demonstrate attomole sensitivity for SARS-CoV-2 nucleocapsid and spike proteins in clinical samples. Untargeted and semi-targeted metabolomics identify metabolic fingerprints of infection and immune activation, guiding biomarker discovery and therapeutic monitoring.

Benefits and Practical Applications

These combined workflows accelerate discovery of viral functional determinants, support rapid biomarker identification for diagnostics, and inform rational design of vaccines and antivirals. High-throughput assays alleviate supply shortages in PCR testing by providing mass spectrometry alternatives. Structural insights drive drug target validation, while metabolomic signatures enable patient stratification and outcome prediction in clinical settings.

Future Trends and Opportunities

Emerging developments include integration of multi-omic datasets with machine learning for predictive modeling of viral behavior, single-particle MS for direct pathogen profiling, and automation of sample processing for pandemic-scale throughput. Advances in ion mobility, data-independent acquisition, and real-time search algorithms will further enhance sensitivity, depth, and speed. Broader adoption of cloud-based analytics promises to democratize access to complex data interpretation and accelerate global collaborative research.

Conclusion

Mass spectrometry–based omic workflows offer unparalleled depth and versatility for comprehensive virus research. By uniting quantitative proteomics, structural biology, targeted detection, and metabolomics on a single technological platform, researchers can rapidly uncover critical viral mechanisms, develop sensitive diagnostics, and drive effective interventions. Continued innovation in instrumentation, reagents, and data analysis will strengthen our capacity to respond to current and future viral threats.

Reference

1. Proteomic and Metabolomic Characterization of COVID-19 Patient Sera Cell 2020 182(1):59-72
2. Multi-organ proteomic landscape of COVID-19 autopsies Cell 2021 184(3):775-791
3. Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs Cell 2021 184(15):3962-3980
4. Autoproteolytic Products of the SARS-CoV-2 Nucleocapsid Protein are Primed for Antibody Evasion and Virus Proliferation bioRxiv 2020
5. Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell Cell Reports 2021 36(2):109364
6. Site-specific glycan analysis of the SARS-CoV-2 spike Science 2020 369(6501):330-333
7. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Nature 2020 583:459-468
8. A mass spectrometry-based targeted assay for detection of SARS-CoV-2 antigen from clinical specimens EBioMedicine 2021 69:103465
9. Large-Scale Multi-omic Analysis of COVID-19 Severity Cell Systems 2021 12(1):23-40
10. Untargeted Metabolomics of COVID-19 patient serum reveals potential prognostic markers medRxiv 2020
11. Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19 Vaccine ACS Central Science 2021 7(4):594-602