How the SARS-CoV-2 viral protein damages the heart

Researchers at the Center for Accurate Disease Modeling at the University of Maryland School of Medicine (UMSOM) have identified how a specific protein in the SARS-CoV-2 virus that causes COVID-19 damages heart tissue
.
They then used a drug to reverse the protein's toxic effects
on the heart.

Their findings are based on studies of fruit flies and mouse heart cells, published in Communications Biology
on September 30, 2022.

People with COVID-19 have a significantly higher
risk of heart muscle inflammation, abnormal heart rhythms, blood clots, strokes, heart attacks, and heart failure for at least a year after infection compared to people who are not infected with the virus.
Although scientists have been quick to develop vaccines and drugs to reduce the severity of COVID-19 disease, these therapies do not protect the heart or other organs from the damage
that even minor infections can cause.

"To treat patients in the long term, we must first understand the mechanisms
that lead to the disease.
Our study shows that a single SARS-CoV-2 protein can cause significant damage to specific tissues in the body, similar to the findings made on other viruses such as HIV and Zika," said
senior author, professor of medicine and director of the Center for Precision Disease Modeling at the University of Michigan School of Medicine.
"By identifying these damaging processes in each tissue, we can test the drugs and see if any drugs can reverse this damage; Those promising drugs can be further tested
in clinical research studies.
”

Last year, Dr.
Han and his team discovered the most toxic SARS-CoV-2 protein
in studies using fruit flies and human cells.
They found a promising drug, selinexor, that reduced the toxicity of one of the proteins, but not another
, called Nsp6.

In their latest study, they found that Nsp6 is the most toxic SARS-CoV-2 protein
in the heart of fruit flies.
Next, they found that the Nsp6 protein hijacked cells in the heart of fruit flies, initiating the glycolysis process that causes the cells to burn glucose for energy
.
Normally, heart cells use fatty acids as an energy source, but in heart failure, these cells switch to sugar metabolism in an attempt to repair damaged tissue
.
The researchers also found that the Nsp6 protein disrupts the cell's powerhouse, the mitochondria, which produce energy through sugar metabolism, which increases damage
.

The team then used 2-deoxyglucose (2DG) to block glucose metabolism
in Drosophila 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 mechanisms of infected animals, altering their metabolism and stealing energy from cells, so we suspect SARS-CoV-2 did something similar
.
" Viruses can also use byproducts of glucose metabolism as building blocks to make more viruses," Dr.
Han said
.
"Therefore, we predict that this drug, which changes the metabolism of the heart to pre-infection, is harmful to the virus because it both cuts off the energy supply to the virus and eliminates the fragments
needed for the virus to replicate.
"

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

Many Americans recovering from COVID develop dangerous heart disease weeks or months later, and we need to understand the root cause of
this happening.
As this study elucidates the pathway of the Nsp6 protein, we can refine our therapeutic goals for future studies, with the ultimate goal of reversing further heart damage
in these patients.
"

SARS-CoV-2 Nsp6 damages Drosophila heart and mouse cardiomyocytes through MGA/MAX complex-mediated increased glycolysis