Proteomics in SARS-CoV-2 Research
The novel coronavirus disease 2019 (COVID-19), a pandemic induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses extreme health threats as well as tremendous economic loss worldwide. To develop therapeutic and preventative strategies, it is critical to understand how the proteins play in the SARS-CoV-2 infection process and disease progression. In this respect, proteomics is able to provide rapid and large-scale viral protein characterization, significantly contributing to understanding host-viral protein interactions, finding biomarkers to monitor the infection course, and exploring the mechanisms of viral pathogenesis. Therefore, proteomics is an indispensable tool in COVID-19 research and its role will be expanded further in the future. Here we give a brief summary of recently proteomic methods on the proteome of SARS-CoV-2.
Several different proteomic methodologies are currently used to study SARS-CoV-2
| Proteomic technique | Study objective |
| H/DX-MS | N protein structure |
| Native mass spectrometry (nMS) | S-ACE2 virus-host protein complex structure; drug mechanism (heparin) |
| Affinity purification-mass spectrometry (AP-MS) | Virus-host protein-protein interactions; drug candidates |
| Proximity-dependent labeling (PDL) | Virus-host proximal protein interactions |
| Phosphoproteomics | Phosphoproteome during infection; drug candidates |
| Targeted proteomics | Diagnostic methods |
| Abundance proteomics | Biomarkers of COVID-19 disease severity |
| Thermal proteome profiling (TPP) | Off-target effects of COVID-19 drug candidates (remdesivir, hydroxychloroquine, and more) |
How can proteomics help to study SARS-CoV-2 biology and COVID-19 pathology?
Determination of dynamic structures of SARS-CoV-2 proteins and virions
Viral proteins determine the structure and shape of the virion and perform the activities necessary for viral replication. In addition to promoting the understanding of protein functions, studying the dynamic structures of SARS-CoV-2 proteins and virions also helps to develop effective small molecule therapies. To achieve this under near-physiological conditions, proteomic approaches have been applied, such as hydrogen/deuterium exchange mass spectrometry (H/DX-MS), cross-linking mass spectrometry (XL-MS), and native MS (nMS). Compared with atomic-resolution structural approaches (e.g., X-ray crystallography and NMR) and cryo-electron microscopy (cryo-EM), these mass spectrometry (MS)-based proteomic structure techniques need relatively fewer protein samples but require a high degree of specialized expertise and equipment.
Characterization of host-virus protein interactions for SARS-CoV-2 infection
Studying virus-host protein interactions can provide mechanistic details into the viral life cycle. Affinity purification-mass spectrometry (AP-MS) is the most widely used proteomics approach to describe virus-host interactions. While proximity-dependent labeling (PDL) coupled to quantitative MS (PDL-MS) is a complementary method to AP-MS, allowing study proximal protein and protein interactions, especially these more transient or weaker interactions. However, the two methods are only used to characterize host interactions of single viral proteins.
Providing diagnostic testing or finding biomarkers to monitor the infection course
Rapid and reliable diagnostics as well as biomarkers to monitor disease progression are required to manage the SARS-CoV-2 pandemic. Besides genomic-based approaches, proteomics is another good strategy for a high volume of diagnostic testing as well as biomarkers discovery of treatment response or disease severity. In addition to identifying druggable targets, these proteomic technologies, including thermal proteome profiling (TPP), limited proteolysis-coupled mass spectrometry (LiP-MS), and activity-based protein profiling (ABPP), can be applied to study the binding of drugs to those targets.
Creative Proteomics is a forward-looking research institute as well as a leading custom service provider in the field of viral proteomics. We are dedicated to providing a series of proteomic techniques to help customers quickly and comprehensively investigate viral proteomics. For more information on how we can help you, please feel free to contact us or directly send us an inquiry.
References
- Haas, P., et al. (2021). "Proteomic approaches to study SARS-CoV-2 biology and COVID-19 pathology." Journal of proteome research, 20(2), 1133-1152.
- Sperk, M., et al. (2020). "Utility of Proteomics in Emerging and Re-Emerging Infectious Diseases Caused by RNA Viruses." Journal of Proteome Research, 19(11), 4259-4274.
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