Study identifies potential pharmacological targets for treating COVID-19-related heart failure

Researchers at the University of Maryland School of Medicine (UMSOM) Center for Precision Disease Modeling have identified how specific proteins in SARS-CoV-2, the virus that causes COVID-19, damage heart tissue. did. Drugs were then used to reverse the toxic effects of that protein on the heart.

Their findings, based on studies with fruit fly and mouse heart cells, will be announced on September 30, 2022. communication biology, Nature journal.

People infected with COVID-19 have a significantly higher risk of developing myocardial inflammation, arrhythmias, blood clots, stroke, heart attack, and heart failure for at least a year after infection than people who are not infected. infected with a virus. Scientists have rapidly developed vaccines and drugs to reduce the severity of COVID-19 disease, but these treatments cannot protect the heart and other organs from damage caused by mild infections. .

To treat patients long-term, we first need to understand the underlying mechanisms of disease. Our study shows that each individual SARS-CoV-2 protein can be highly damaging to specific tissues in the body. Similar to those found in other viruses such as HIV and Zika. By identifying these damaging processes in each tissue, drugs can be tested to see if they can reverse this damage. Promising drugs can be further tested in clinical studies. ”

Zhe Han, senior author of the study and Professor of Medicine, University of Maryland School of Medicine

Dr. Han is also Director of UMSOM’s Center for Precision Disease Modeling.

Last year, Dr. Han and his research team identified the most virulent SARS-CoV-2 protein in studies using fruit flies and human cells.they found a promising drug Selinexor The toxicity of one of these proteins was reduced, but not the other protein known as Nsp6.

Their latest study found Nsp6 to be the most virulent SARS-CoV-2 protein in the fly heart. They then found that the Nsp6 protein hijacks the cells of the fruit fly’s heart to turn on the glycolytic process. Normally, heart cells use fatty acids as an energy source, but when heart failure occurs, these cells switch to glucose metabolism as they attempt to repair damaged tissue. It was discovered that it does additional damage by destroying the cell’s powerhouses called mitochondria that generate energy from.

The team then used the drug 2-deoxy-D-glucose (2DG) to block sugar metabolism in fruit fly and mouse heart cells. They found that the drug reduced heart and mitochondrial damage caused by the Nsp6 viral protein.

“We know that some viruses hijack the cellular machinery of infected animals to alter their metabolism and steal their energy sources, so SARS-CoV-2 is doing the same. Viruses are more viruses using the by-products of sugar metabolism as building blocks,” Dr. Han said. “Therefore, we predict that this drug, which restores the heart’s metabolism to its pre-infection state, will adversely affect the virus by shutting off its energy supply and eliminating fragments necessary for replication.”

Fortunately, 2DG is cheap and routinely used in laboratory studies, researchers say. Although 2DG has not been approved by the US Food and Drug Administration as a treatment for any disease, the drug is currently undergoing clinical trials in India as a treatment for COVID-19.

“Too many Americans recovering from COVID are going to have dangerous heart disease weeks or months later. We need to learn the underlying reasons why this is happening,” says Mark T. Gladwin. , MD said., John Z. and Akiko K. Bowers Distinguished Professor and Dean, UMSOM, Vice President for Medical Affairs at the University of Maryland Baltimore. Ultimately, it will allow us to improve targeted treatments for future research.”