Researchers 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 has shown that they also play a key role in the disease itself.
The paper, published in Circulation Research, has also shown 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 and cells treated with the SARS-CoV-2 Spike protein have shown that the spike protein causes increased mitochondrial fragmentation in vascular cells.
The study is a collaboration between Salk Institute and University of California San Diego.
The paper has provided 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, researchers 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 have shown that the spike protein damaged the cells by binding ACE2. This binding disrupted ACE2’s molecular signaling to mitochondria, 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.
Further studies with mutant spike proteins will also provide new insight towards the infectivity and severity of mutant SARS CoV-2 viruses. ( Xagena )
Source: Salk Institute, 2021