In patients with severe and long-standing Covid-19, blood coagulation disorders have often been observed. Now researchers at Linköping University (LiU) in Sweden have found that immune system can affect the spike protein on the surface of the SARS-CoV-2 virusleading to the production of a misfolded spike protein amyloid call.
Those who suffer from Covid-19 in a serious and prolonged way, can see how other organs, in addition to the lungs, are seriously affected. Complex symptoms and damage may persist, in the heart,the kidneys, eyes, nose, and brain, as well as alterations in blood coagulation. Why the disease affects the body in this way is largely a mystery.
Now, LiU researchers have found a biological mechanism that had never been described and that may be part of the explanation.
This team studies diseases caused by misfolded proteins, of which Alzheimer’s disease is the best known example. The researchers noted that there are many similarities between symptoms related to Covid-19 and those seen in diseases caused by proteins. poorly folded.
The functions of proteins are greatly affected by the fact that they fold in specific ways that give rise to a concrete three-dimensional structure. In addition to this form, a protein can also take an alternate form. More than 30 different proteins are known to have this type of alternative form, which is associated with disease.
This alternatively folded protein is called amyloid. LiU researchers wondered if the virus that causes Covid-19, SARS-CoV-2, contains a protein that can create amyloid. Specifically, they were interested in the “spike” protein on the surface of the virus, which it uses to interact with the body’s cells and infect them.
Using a computer simulation, the researchers discovered that lThe spike protein of the coronavirus contained seven different sequences that could produce amyloid. Three of the seven sequences met the investigators’ criteria for being considered amyloid-producing sequences when tested experimentally. They produced, among other things, so-called fibrils, which look like long threads when examined under an electron microscope.
But do these fibrils arise spontaneously? It is well known that many diseases, such as Alzheimer’s, are preceded by a process in which the body cuts large proteins into smaller pieces, which in turn can produce harmful amyloid. In their study, they show that an enzyme in the white blood cells of the immune system can cut the spike protein of the coronavirus.
When the spike protein is cut, it produces the exact piece of protein that, according to the researchers’ analysis, is most likely to produce amyloid. This enzyme is released in large quantities from a type of white blood cell, neutrophils, which are released early in infections such as Covid-19.
When the researchers mixed pure spike protein with this enzyme, called neutrophil elastase, unusual fibrils were produced.
“We have never seen fibrils as perfect, but terrifying, as these of the spike protein of SARS-CoV-2, which produces amyloid, and its pieces. The fibrils that start from the full-size spike protein branch out like the limbs of a body. Amyloids don’t usually branch like this. We think it’s due to the characteristics of the spike protein,” he says. Per Hammarströmprofessor of Department of Physics, Chemistry and Biology (IFM) from Linkoping University.
Previous research has indicated that the spike protein may be involved in the production of small blood clots.
the blood contains fibrin proteinwhich helps blood to clot when a vessel is damaged, so that the hole reseals itself and the bleeding stops.
When the lesion has begun to heal, the thrombus is supposed to be broken up by plasmin, which is also found in the blood. The LiU researchers mixed pieces of amyloid-producing protein with these body substances in test tubes, and found that the resulting fibrin clot could not be broken down by plasmin in the usual way. This newly discovered mechanism may be behind the production of blood microcoagules similar that have been observed in both severe and long-term Covid-19.
“We see that the spike protein, when affected by our own immune system, can produce amyloid structures, and that this can potentially affect our blood coagulation. We believe this discovery is important to many fields of research, and we hope that other researchers will examine the questions it raises,” he says. Sofie Nyströmwho is an associate professor at the IFM and the other author of the study.