How the SARS-CoV-2 protein affects vascular function

Since coronavirus disease (COVID-19) continues to spread, it is presumed that it is also a vascular disease. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects the body across the respiratory tract, causing a variety of symptoms and complications.

Researchers at Tel Aviv University sought to identify how certain SARS-CoV-2 proteins affect the vascular system. They found that 70% of SARS-CoV-2 proteins affect vascular permeability, specifically targeting endothelial cells.

Survey published on preprint server medRxiv*, It is possible to identify and isolate how each SARS-CoV-2 protein independently affects the endothelial response and directly measure endothelial function.

Effect of SARS-CoV-2 protein on endothelial cells. A sketch showing the major organs affected by SARS-CoV-2. Structure and gene composition of bSARS-CoV-2.

SARS-CoV-2 and vascular system

COVID-19 causes serious illness in high-risk populations such as the elderly and those with comorbidities.Often severe illness Cytokine storm, Vascular dysfunction, progressive lung injury, and coagulation.

SARS-CoV-2 affects several important organs such as lungs, heart, kidneys and blood vessels through pathological effects on endothelial cells.

In previous studies, COVID-19 can cause serious illness. After the initial viral infection stage, about 30% of 40 hospitalized patients develop severe illness with progressive lung injury and a severe immune response. As a result, other complications such as hypoxia in the blood and cytokine storms were observed. These led to heart and kidney damage.

Many of these conditions were associated with increased coagulation and vascular dysfunction. It is believed that COVID-19 is not only a respiratory illness, but may also be a vascular disease. It causes leakage of the vascular barrier and increased expression of von Willebrand factor (VWF), leading to increased coagulation, inflammation and cytokine release.

Changes in the endothelial barrier of blood vessels can be due to several factors. First, it can be the result of direct effects on endothelial cells, causing dermatitis and endothelial dysfunction. Second, it can be due to lysis and death of endothelial cells.

Third, it may be due to the sequestration of human angiotensin converting enzyme 2 (hACE2) by a viral protein that stimulates the kallikrein-bradykinin renin-angiotensin pathway and promotes vascular permeability.

Finally, an overreaction of the immune system that results in a combination of immune cells and neutrophils. This produces reactive oxygen species, inflammatory cytokines, and vasoactive molecules.

In addition, hyaluronic acid deposition causes changes in endothelial binding, increasing vascular permeability, leakage, and coagulation.

the study

The SARS-CoV-2 genome encodes 29 proteins, contributes to disease signs and symptoms, and endothelial complications are unknown.

To determine the effect of these proteins on endothelial cells, the team cloned and expressed 26 of these proteins into human cells, especially human umbilical vein endothelial cells (HUVEC). They observed the endothelial response to overexpression of each protein.

The team found that 70% of these proteins stimulated significant changes in endothelial permeability. Specifically, the proteins nsp2, nsp5_c145a (catalyzed mutant of nsp5), and nsp7 reduced CD31, called platelet endothelial cell adhesion molecule 1 (PECAM-1). It is believed to be a sensitive and specific marker of vascular differentiation. They also increase von Willebrand factor expression and interleukin-6 (IL-6), suggesting endothelial dysfunction.

In addition, the team applied protein-protein interaction (PPI) network analysis to predict endothelial proteins affected by viral proteins. They used the PPI model to determine the role of each protein in other tissues affected by SARS-CoV-2.

Overall, this study identified the most dominant viral proteins that influence the physiological response of the virus. The team believes that this study provides better insight into the mechanism by which the vascular system responds to SARS-CoV-2 infection. From there, the team recommends that the findings may serve as the basis for drug development targeting identified proteins.

The virus has spread to 192 countries and territories and has infected more than 114 million people, so finding an effective drug is essential. The virus kills 2.54 million people worldwide.

The country with the highest number of cases includes the United States, which has 28.71 million cases. India, 11.12 million cases. In Brazil, there are 10.64 million cases.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.