Researchers Identify Proteins in the Coronavirus That Can Damage Blood Vessels

Covid in blood vessel. Credit: Tel Aviv University

Nearly two years since it became a global pandemic that killed millions of people, the mystery of which proteins in the SARS-CoV-2 virus are responsible for severe vascular damage that can even lead to a heart attack or stroke has not been solved. Now, for the first time, a team of experts led by Tel Aviv University is able to identify 5 of the 29 proteins that make up the virus and are responsible for damaging blood vessels. The researchers hope the identification of these proteins will help develop targeted drugs for COVID-19 that reduce vascular damage.

The study was led by Dr. Ben Maoz from the Department of Biomedical Engineering and Sagol School of Neuroscience, Prof. Uri Ashery from the Wise Faculty of Life Sciences and Sagol School of Neuroscience, and Prof. Roded Sharan from the Blavatnik School of Computer Science – all researchers from Tel Aviv University. Also participating in the study were Dr. Rossana Rauti, Dr. Yael Bardoogo, and doctoral student Meishar Shahoah from Tel Aviv University and Prof. Yaakov Nahmias of the Institute of Life Sciences at the Hebrew University. The results of the new study are published in the journal eLife.

Dr Ben Maoz. Credit: Tel Aviv University

“We see a very high incidence of vascular disease and blood clotting, for example stroke and heart attack, among COVID patients,” says Dr Ben Maoz. “We tend to think of COVID as primarily a respiratory disease, but the truth is that coronavirus patients are up to three times more likely to have a stroke or heart attack. All the evidence shows that the virus severely damages the blood vessels or the endothelial cells that line the blood vessels. To this day, however, the virus is treated as one entity. We wanted to know which proteins in the virus are responsible for this type of damage.”

The new coronavirus is a relatively simple virus — it contains a total of 29 different proteins (compared to the tens of thousands of proteins made by the human body). The Tel Aviv University researchers used the RNA from each of the COVID-19 proteins and examined the response that occurred when the different RNA sequences were introduced into human blood vessel cells in the lab; this allowed them to identify five coronavirus proteins that damage blood vessels.

Prof. dr. Uri Ashery. Credit: Tel Aviv University

“When the coronavirus enters the body, it starts producing 29 proteins, a new virus is formed, that virus produces 29 new proteins, and so on,” explains Dr. Maoz out. “During this process, our blood vessels change from opaque tubes to a kind of permeable nets or pieces of cloth, and at the same time there is an increase in blood clotting. We thoroughly examined the effect of each of the 29 proteins expressed by the virus and were successful in identifying the five specific proteins that cause the greatest damage to endothelial cells and thus to vascular stability and function. In addition, we used a computational model developed by Prof. Sharan that allowed us to assess and identify which coronavirus proteins have the greatest effect on other tissues, without seeing them ‘in action’ in the lab.”

According to Dr. Maoz, the identification of these proteins could have major consequences in the fight against the virus. “Our research may help find targets for a drug that will be used to stop the activity of the virus, or at the very least minimize damage to blood vessels.”

Reference: “Effect of SARS-CoV-2 proteins on vascular permeability” by Rossana Rauti, Meishar Shahoha, Yael Leichtmann-Bardoogo, Rami Nasser, Eyal Paz, Rina Tamir, Victoria Miller, Tal Babich, Kfir Shaked, Avner Ehrlich, Konstantinos Ioannidis, Yaakov Nahmias, Roded Sharan, Uri Ashery and Ben Meir Maoz, October 25, 2021, eLife.
DOI: 10.7554 / eLife.69314