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Thursday, May 06, 2021

New research: Besides initiating infection, coronavirus spike protein has key role in illness

The paper also finds that Covid-19 is a vascular disease, demonstrating exactly how the SARS-CoV-2 virus damages and attacks the vascular system (comprising the blood vessels) on a cellular level.

By: Express News Service | New Delhi |
Updated: May 1, 2021 9:27:01 am
A woman tests for Covid-19 in Lucknow. (Express Photo: Vishal Srivastav)

Scientists have known for a while that SARS-CoV-2’s spike proteins help the virus infect its host by latching on to healthy cells. Now, a major new study shows that the spike proteins also play a key role in the disease itself.

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The paper, published on April 30 in the journal Circulation Research, also finds that Covid-19 is a vascular disease, demonstrating exactly how the SARS-CoV-2 virus damages and attacks the vascular system (comprising the blood vessels) on a cellular level.

The findings help explain Covid-19’s wide variety of seemingly unconnected complications, and could open the door for new research into more effective therapies, the Salk Institute said in a media release. Salk researchers collaborated with scientists at the University of California San Diego on the paper.

“A lot of people think of it as a respiratory disease, but it’s really a vascular disease. 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,” the Salk Institute quoted Professor Uri Manor, co-senior author of the study, as saying.

There’s been a growing consensus that SARS-CoV-2 affects the vascular system, but exactly how it did so was not understood. Similarly, scientists studying other coronaviruses have long suspected that the spike protein contributed to damaging vascular endothelial cells, but this is the first time the process has been documented. So, the findings themselves aren’t entirely a surprise. But the paper provides for the first time clear confirmation and a detailed explanation of the mechanism through which the protein damages vascular cells, the Salk Institute said.

In the new study, the researchers created a “pseudovirus” that was surrounded by SARS-CoV-2 classic crown of spike proteins, but did not contain any actual virus. Exposure to this pseudovirus resulted in damage to the lungs and arteries of an animal model—proving that the spike protein alone was enough to cause disease. Tissue samples showed inflammation in endothelial cells lining the pulmonary artery walls.

The team then replicated this process in the lab, exposing healthy endothelial cells (which line arteries) to the spike protein. They showed that the spike protein damaged the cells by binding ACE2 (a human protein). This binding disrupted ACE2’s molecular signalling to mitochondria (organelles that generate energy for cells), causing the mitochondria to become damaged and fragmented.

Previous studies have shown a similar effect when cells were exposed to the SARS-CoV-2 virus, but this is the first study to show that the damage occurs when cells are exposed to the spike protein on its own, the Salk Institute said.

“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. Further studies with mutant spike proteins will also provide new insight towards the infectivity and severity of mutant SARS CoV-2 viruses,” Manor was quoted as saying.

Source: Salk Institute

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