Effect of SARS-CoV-2 proteins on vascular permeability
The study, “Effect of SARS-CoV-2 proteins on vascular permeability,” examines how individual proteins encoded by the SARS-CoV-2 genome impact endothelial cells and contribute to COVID-19’s vascular complications.
Here’s a detailed summary:
Title: Effect of SARS-CoV-2 proteins on vascular permeability
- To determine how specific SARS-CoV-2 proteins affect endothelial cells.
- To understand the role of these proteins in vascular dysfunction associated with COVID-19.
- The study cloned and expressed 26 of the 29 proteins encoded by SARS-CoV-2 in human cells.
- It assessed the endothelial response to the overexpression of each protein, focusing on changes in endothelial permeability and inflammation.
- Impact on Endothelial Permeability: 18 of the 26 SARS-CoV-2 proteins significantly altered endothelial barrier integrity. The most notable changes were observed with proteins nsp5_c145a, nsp13, nsp7, orf7a, and nsp2, which caused a 20–28% decrease in trans-epithelial-endothelial electrical resistance (TEER) values, indicating increased permeability.
- Increased Inflammatory Response: Proteins nsp2, nsp5_c145a, and nsp7 not only impacted barrier function but also induced an upregulated expression of the coagulation factor von Willebrand factor (VWF) and cytokine release, notably interleukin-6 (IL-6). This suggests a role in the inflammatory response and coagulation-related pathologies seen in COVID-19.
- Protein-Protein Interaction (PPI) Network Analysis: A PPI network was used to predict which endothelial proteins are most affected by SARS-CoV-2 proteins. The analysis revealed that tight junction proteins like cadherin-5, ZO-1, and β-catenin are significantly impacted, especially by nsp2, nsp5_c145a, and nsp7.
- Systemic Implications: The study’s findings suggest that vascular dysfunction plays a significant role in the progression of COVID-19. While the exact mechanism of how the virus affects the vasculature is unclear, the study reveals the potential systemic impact of these interactions, including vasculature leakiness and potential exotoxicity.
- The study highlights the importance of vascular aspects in COVID-19, identifying key SARS-CoV-2 proteins that significantly affect endothelial barrier function and inflammatory responses.
- It also underscores the utility of PPI network analysis in understanding the interaction between viral and human proteins, providing insights that could expedite drug development targeting these specific viral proteins.
This research offers a comprehensive view of how SARS-CoV-2 proteins individually contribute to vascular complications in COVID-19, shedding light on potential targets for therapeutic intervention.
Read More: https://elifesciences.org/articles/69314