[D66] [JD: 97] The novel coronavirus’ spike protein plays additional key role in illness - COVID-19 is a VASCULAR disease

[R.O.]

Het wordt steeds bonter:

https://www.salk.edu/news-release/the-novel-coronavirus-spike-protein-plays-additional-key-role-in-illness/
https://www.youtube.com/watch?v=fMjPtDK8evg

April 30, 2021
The novel coronavirus’ spike protein plays additional key role in illness

Salk researchers and collaborators show how the protein damages cells,
confirming COVID-19 as a primarily vascular disease

Home - Salk News - The novel coronavirus’ spike protein plays additional
key role in illness
Salk News

April 30, 2021
The novel coronavirus’ spike protein plays additional key role in illness

Salk researchers and collaborators show how the protein damages cells,
confirming COVID-19 as a primarily vascular disease

LA JOLLA—Scientists have known for a while that SARS-CoV-2’s distinctive
“spike” proteins help the virus infect its host by latching on to
healthy cells. Now, a major new study shows that the virus spike
proteins (which behave very differently than those safely encoded by
vaccines) also play a key role in the disease itself.

The paper, published on April 30, 2021, in Circulation Research, also
shows conclusively that COVID-19 is a vascular disease, demonstrating
exactly how the SARS-CoV-2 virus damages and attacks the vascular system
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.
Representative images of vascular endothelial control cells (left) and
cells treated with the SARS-CoV-2 Spike protein (right) show that the
spike protein causes increased mitochondrial fragmentation in vascular
cells.
Click here for a high-resolution image.
Credit: Salk Institute

“A lot of people think of it as a respiratory disease, but it’s really a
vascular disease,” says Assistant Research Professor Uri Manor, who is
co-senior author of the study. “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.”

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.

While the findings themselves aren’t entirely a surprise, the paper
provides clear confirmation and a detailed explanation of the mechanism
through which the protein damages vascular cells for the first time.
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.

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. This
binding disrupted ACE2’s molecular signaling 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.

“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.”

The researchers next hope to take a closer look at the mechanism by
which the disrupted ACE2 protein damages mitochondria and causes them to
change shape.

Other authors on the study are Yuyang Lei and Zu-Yi Yuan of Jiaotong
University in Xi’an, China; Cara R. Schiavon, Leonardo Andrade, and
Gerald S. Shadel of Salk; Ming He, Hui Shen, Yichi Zhang, Yoshitake Cho,
Mark Hepokoski, Jason X.-J. Yuan, Atul Malhotra, Jin Zhang of the
University of California San Diego; Lili Chen, Qian Yin, Ting Lei,
Hongliang Wang and Shengpeng Wang of Xi’an Jiatong University Health
Science Center in Xi’an, China.

The research was supported by the National Institutes of Health, the
National Natural Science Foundation of China, the Shaanxi Natural
Science Fund, the National Key Research and Development Program, the
First Affiliated Hospital of Xi’an Jiaotong University; and Xi’an
Jiaotong University.

DOI: 10.1161/CIRCRESAHA.121.318902