The heart-damaging SARS-CoV-2 protein has been found!

Since the beginning of the pandemic, scientists have documented the "spectrum"
of SARS-CoV-2's potential effects on the heart.
Now, a team of researchers at the University of Maryland has discovered that a specific viral protein can damage the heart — at least in fruit flies and mice
.

When a virus enters a host cell, it induces that cell to produce a specific viral protein
.
The SARS-CoV-2 virus contains genetic information about 29 different proteins, and in a paper published in September in the journal Biology of Communications, researchers determined that one of these proteins, Nsp6, increases the energy use
of heart cells in a way that can cause heart damage.

The researchers first selected 12 proteins that were most likely to trigger a pathogenic response in host cells and identified
them by computational methods that predicted their function based on structure.
The team then designed 12 different Drosophila cell lines, each expressing a protein in their heart cells, and looked at the effects
of these proteins on mortality, the morphology of the flies' hearts, and gene expression in the heart cells.

They found that a protein called Nsp6 had particularly harmful effects — the GM Nsp6 had a much higher mortality rate in fruit flies than control flies and, according to the paper, showed "significant structural and functional damage" to their hearts.

In addition, protein genes involved in glycolysis (the breakdown of glucose into usable energy) were upregulated
in muscle heart cells or cardiomyocytes of Nsp6 fruit flies.
Overloaded glycolysis disrupts the function
of mitochondria within cardiomyocytes where part of the glycolysis step takes place.
Ultimately, the destruction of mitochondria led to heart failure
in fruit flies, the researchers wrote in the study.

Zhe Han, a developmental biologist at the University of Maryland and co-author of the study, hypothesized that upregulation of glycolysis is a problem for viral survival — it forces cells to provide more fuel
for viral replication.
Professor Han said that because cardiomyocytes are very similar to other muscle cells, the muscle pain and weakness experienced by COVID-19 patients may also be related
to the upregulation of glycolysis caused by Nsp6.

The team also found that the Nsp6 protein upregulated glycolysis
in mouse heart cells grown in the lab.
Proteins involved in glycolysis are highly conserved between fruit flies and mammals, Han said, so these results may provide assistance
in understanding how SARS-CoV-2 damages the human heart.
The authors also tested a possible treatment, a compound called 2-deoxy-D-glucose (2DG), which can reduce glycolysis
.
They found that it mitigated the harmful effects
of Nsp6 in animal cells.

Paul Cheng, a cardiologist at Stanford University School of Medicine who was not involved in the study, said that while it's an "interesting hypothesis" that SARS-CoV-2's Nsp6 causes heart damage, there may be other causes of this damage after infection, such as myocarditis, which describes inflammation of the heart and does not address the pathways
described in the paper.
Han acknowledges that heart damage can have multiple causes
.
"The immune response may also trigger some kind of stress
in the organs," he said.
”

In addition, Cheng said, it is unclear to what extent SARS-CoV-2 can enter cardiomyocytes
.
"Cardiomyocytes themselves do not appear to have a large number of key receptors
that express the SARS-CoV-2 virus," Cheng said.
He was referring to a protein
called ACE2.
"There are still many unknowns" about the extent to which SARS-CoV-2 can enter cardiomyocytes; Although cardiomyocyte expression of ACE2 is indeed low, SARS-CoV-2 has been documented to enter cardiomyocytes
.

In any case, there could be another coronavirus pandemic
at some point in the future.
While the spike protein of the virus is often mutated, other proteins remain similar
in coronaviruses.
Well, the next novel coronavirus to infect humans may have a different spike protein but may retain other proteins such as Nsp6, meaning that any understanding of SARS-CoV-2 and how its protein affects health may help fight it
.