The global pandemic caused by the SARS-CoV-2 virus that has killed five million people and infected hundreds of millions so far has been going on for nearly two years. However, scientists around the world have been confused about which specific proteins in the virus are responsible for severe vascular damage that could lead to heart attack or stroke. 

Now, for the first time, a team of experts led by Tel Aviv University (TAU) has been able to identify five of the 29 proteins that make up the virus that are responsible for damaging blood vessels. The researchers hope that 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 of the department of biomedical engineering and Sagol School of Neuroscience; Prof. Uri Ashery of the Wise Faculty of Life Sciences and Sagol School of Neuroscience, and Prof. Roded Sharan of the Blavatnik School of Computer Science – all TAU researchers. Also participating in the study were Dr. Rossana Rauti, Dr. Yael Bardoogo, and doctoral student Meishar Shahoah of TAU and Prof. Yaakov Nahmias of the Institute of Life Sciences at the Hebrew University of Jerusalem. The results of the new study were published in the journal eLife under the title “Effect of SARS-CoV-2 proteins on vascular permeability.” 

“After the initial phase of the viral infection, ~ 30% of patients hospitalized with COVID-19 develop severe disease with progressive lung damage, known as severe acute respiratory syndrome (SARS), and a severe immune response. Interestingly, additional pathologies have been observed, such as hypoxemia and cytokine storm which, in some cases, lead to heart and kidney failure, and neurological symptoms. Recent observations suggest that these pathologies are mainly due to increased coagulation and vascular dysfunction,” they wrote. 

“We see a very high incidence of vascular disease and blood clotting, for example stroke and heart attack, among COVID patients,” said 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. However, to this day the virus has been treated as one entity. We wanted to find out which proteins in the virus are responsible for this type of damage.”

The new coronavirus is a relatively simple one, comprised of 29 different proteins – compared to the tens of thousands of proteins produced by the human body. The TAU-led team used the RNA of each of the COVID-19 proteins and examined the reaction that occurred when the various RNA sequences were inserted into human blood vessel cells in the lab; they were thereby able to identify five coronavirus proteins that damage the blood vessels.

“When the coronavirus enters the body, it begins to produce 29 proteins, a new virus is formed, that virus produces 29 new proteins, and so on,” explained Maoz. “In this process, our blood vessels turn from opaque tubes into kind of permeable nets or pieces of cloth, and in parallel there is an increase in blood clotting. We thoroughly examined the effect of each of the proteins expressed by the virus and were successful in identifying the five specific proteins that cause the greatest damage to endothelial cells and hence to vascular stability and function. In addition, we used a computational model developed by Prof. Sharan that enabled us to assess and identify which coronavirus proteins have the greatest effect on other tissues, without having seen them ‘in action’ in the lab.”

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