How SARS-CoV-2 proteins affect biologic activity

As the coronavirus infection (COVID-19) spreads, it has also been proven to be a vascular disease. The very severe respiratory coronavirus 2 (SARS-CoV-2) syndrome affects the body outside the respiratory tract, leading to a number of symptoms and complications.

Researchers at Tel Aviv University were trying to identify how SARS-CoV-2-specific proteins affect the vasculature. They found that 70 percent of SARS-CoV-2 proteins induce vascular remodeling, specifically targeting endothelial cells.

The scan, published on the pre-print server medRxiv *, able to identify and isolate how each of the SARS-CoV-2 proteins independently influences endothelial response and directly measures endothelial activity.

SARS-CoV-2 and the vascular system

The COVID-19 leads to severe disease in high-risk populations such as the elderly and those with comorbidities. Often, severe disease is associated with cytokine storm, vascular dysfunction, progressive lung damage, and coagulation.

SARS-CoV-2 affects several vital organs, such as the lungs, heart, kidneys and blood vessels, through its pathological effect on endothelial cells.

In a previous study, COVID-19 could cause severe infection. After the first stage of viral infection, about 30 percent of 40 patients in the hospital develop a serious illness, with progressive lung damage and a poor immune response. As a result, other complications were observed, including low oxygen in the bloodstream and cytokine. These caused heart and kidney failure.

Many of these pathologies were associated with increased coagulation and vascular dysfunction. It is believed that, in addition to being a respiratory illness, COVID-19 may also be a viral infection. It causes leaky vascular obstruction and elevated expression of von Willebrand factor (VWF), responsible for increased coagulation, inflammation, and cytokine release.

Alteration of the endothelial barrier in the blood vessels may be due to a number of factors. First, this may be due to a direct effect on the endothelial cells, causing endothelitis and endothelial dysfunction. Second, this may be due to lysis and death of endothelial cells.

Third, this may be due to the uptake of the human angiotensin-converting enzyme 2 (hACE2) by viral proteins that stimulate kallikrein-bradykinin renin-angiotensin pathways, promoting vascular remodeling.

Finally, there is too much reactivation of the immune system, where a combination of immune cells and neutrophils occurs. This causes the production of reactive oxygen species, inflammatory cytokines, and vasoactive molecules.

Further, hyaluronic acid deposition causes altered endothelial pathways, increasing vascular remodeling, leakage, and coagulation.

The study

The SARS-CoV-2 genome encodes 29 proteins, contributing to the signs and symptoms of the disease, and endothelial dysfunction is unknown.

To see the effect of these proteins on endothelial cells, the team cloned and expressed 26 of these proteins in human cells, specifically human umbilical vein endothelial cells (HUVEC). They monitored the endothelial response to overexpression of each protein.

The team found that 70 percent of these proteins induced significant changes in endothelial permeability. In particular, proteins reduced nsp2, nsp5_c145a (catalytic dead mutant of nsp5), and nsp7 CD31, known as platelet endothelial cell adhesion molecule 1 (PECAM-1), which was thought to be a sensitive and specific marker for inter- vascular separation. They also increased von Willebrand factor expression and interleukin-6 (IL-6), suggesting endothelial dysfunction.

Further, the team performed their protein-protein interaction (PPI) network analysis and predicted the endothelial proteins affected by viral proteins. They used the PPI model to determine the role of each protein in other cigarettes affected by SARS-CoV-2.

Overall, the study identified which viral proteins are most influential in the physiological response of the virus. The team believes the study will provide a better insight into the mechanisms by which the viral system responds to SARS-CoV-2 infection. From there, the team suggests that the findings could form the basis for drug development to target the proteins identified.

Finding an effective drug is crucial as the virus has spread to 192 countries and regions, affecting more than 114 million people. The virus has claimed 2.54 million lives worldwide.

Countries with the highest number of cases include the United States, with 28.71 million cases; India, 11.12 million cases; and Brazil, with 10.64 million cases.

* Important message

medRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.