SARS-COV-2’s distinctive “spike” proteins are known to infect its host by latching onto healthy cells, however, a major new study shows that they also play a key role in the disease itself.
Salk researchers collaborated with scientists at the University of California San Diego on the paper, including co-first author Jiao Zhang and co-senior author John Shyy, among others. The study was published on March 31, 2021, in the journal Circulation Research, showing how the spike protein damages cells – confirming that COVID-19 is primarily a vascular disease.
In the past 16 months, doctors have seen a vast array of seemingly unconnected complications in people infected with COVID-19. The Economic Times is reporting that this new study may open the door for new research into more effective therapies.
“A lot of people think of it as a respiratory disease, but it’s really a vascular disease,” said Uri Manor, Assistant Research Professor at the Salk Institute in California.
“That could explain why some people have strokes, and why some people have issues in other parts of the body. The commonality between them is that they all have vascular underpinnings,” Manor added.
The findings are not entirely a surprise because there has been a growing consensus that the coronavirus somehow affects the vascular system, but how it did this was not fully understood. However, the paper provides clear confirmation and a detailed explanation of the mechanism through which the protein damages vascular cells for the first time.
Basically, the study shows the role the spike protein plays in damaging vascular endothelial cells. To demonstrate how this worked, the researchers created a “pseudovirus” that was surrounded by SARS-CoV-2 classic crown of spike proteins, but did not contain any actual virus.
The pseudovirus was administered intratracheally into animal models, with exposure resulting in damage to the lungs and arteries. This proved the spike protein alone was enough to cause disease. Tissue samples showed inflammation in endothelial cells lining the pulmonary artery walls, reports SciTech Daily.
The scientists then replicated the study in the laboratory, exposing healthy endothelial cells (which line arteries) to the spike protein. This showed that “the spike protein damaged the cells by binding ACE2. This binding disrupted ACE2’s molecular signaling to mitochondria (organelles that generate energy for cells), causing the mitochondria to become damaged and fragmented,” according to the study.
“If you remove the replicating capabilities of the virus, it still has a major damaging effect on the vascular cells, simply by virtue of its ability to bind to this ACE2 receptor, the S protein receptor, now famous thanks to COVID,” Manor explains. “Further studies with mutant spike proteins will also provide new insight towards the infectivity and severity of mutant SARS CoV-2 viruses.”
