How does COVID-19 work?
As many of us start to envision a post-pandemic world, there is still so much thought and scientific effort being poured into understanding the virus that has precluded the world from normalcy.
Often, viruses are explained as follows: upon infection, the virus hijacks the cellular machinery to replicate itself and promptly exits the cell to perpetuate the cycle. However, this barely grazes the surface of what is occurring on the molecular level when it comes to infection. Our bodies have ornate, dynamic systems that constantly work to prevent infection, so why does COVID-19 pose such an intractable challenge for the robust human immune system?
Many scientists have developed approaches to study this, and these approaches can be a means of finding pharmaceuticals to be co-opted for use in fighting infection. They first take a look at the symptoms being presented and the biology of the organism, and then target the infection by either:
Mitigating symptoms that were induced by the ‘hijacking’ of cellular machinery, or
Assaulting the physiology of the virus itself in a way that does not harm our own cells.
Alexey Stukalov and coworkers recently published their results of a multilevel proteomics study characterizing the virus-host interactions at the protein level. Proteomics is the study of the proteome, the complete set of proteins a cell makes under a specific condition—the condition here being infection with either SARS-CoV (SCV—SARS-associated coronavirus) or SARS-CoV-2 (SCV2—the coronavirus causing COVID-19) (Stukalov et al.).
To characterize the proteome of infected cells, the authors performed mass spectrometry on samples of cells that had been infected with either coronavirus. Mass spectrometry is a common analytical tool in chemistry and biology and it operates by ‘exploding’ the cell into its various components and observing how these pieces interact with a magnetic field. This technique then allows scientists to characterize the signature of each cellular component and perform quantitative analysis (Stukalov et al.).
First, the authors noted an SCV2-specific interaction between ORF8, an SCV2 protein, and TGF-𝛽, a protein implicated in modulating the immune system. Stukalov and coworkers claimed this interaction might contribute to the increased pathogenicity of SCV2 (Stukalov et al.).
Another common phenomenon was the increased ubiquitination (a process that marks proteins for degradation) of proteins facilitating autophagy and endothelial integrity (Stukalov et al.). Autophagy refers to the process of a cell ‘eating’ itself to degrade unwanted components, including pathogens; endothelial integrity refers to the structural soundness of blood vessels and other anatomical plumbing.
These findings correlate well with many of the clinical presentations of severe COVID-19. The authors also note that many of these virus-host cell interactions aided in the viral replication process and contributed to fibrosis, or the formation of scar tissue in the lungs (Stukalov et al.). While these results seem bleak, they do open the door for targeted therapy.
Finally, Stukalov and coworkers treated cells infected with COVID-19 using their pinpointed knowledge of how the virus assaults the native biology. Unsurprisingly, their dataset proved valuable and they located viable drug candidates after observing significant antiviral activity through their screening of forty-eight potential pharmaceuticals (Stukalov et al.). Although we can see a glimpse of light at the end of the pandemic tunnel, work like this continues to be important as we face the reality of COVID-19 becoming just as periodic and mundane as the common flu.
Stukalov, A., Girault, V., Grass, V. et al. “Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV.” Nature, 12 April 2021, https://doi.org/10.1038/s41586-021-03493-4.
Last Fact Checked on May 22nd, 2021.