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

Key Objectives:

  • 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.

Methodology:

  • 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.

Findings:

  1. 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​​.
  2. 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​​.
  3. 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​​.
  4. 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​​.

Conclusions:

  • 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

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