Washington, Nov 8, 2022: 2DG, a drug developed by the Indian defence unit Defence Research and Development Organisation (DRDO) may reverse the heart damage caused by a protein in the SARS-CoV-2 virus, a study conducted in fruit flies and mice has found.
Researchers from the University of Maryland identified how a specific protein in SARS-CoV-2, the virus responsible for COVID-19, damages heart tissue. They then used the drug, called 2DG, to reverse the toxic effects of that protein on the heart.
Developed by Dr Reddy’s Laboratories in collaboration with DRDO, 2DG is an oral drug. The SARS-CoV-2 virus depends upon glycolysis or breakdown of glucose for energy. The drug hinders the process of glycolysis and prevents the growth of the virus.
“Our research shows that individual SARS-CoV-2 proteins can each do major damage to specific tissues in the body – similar to what has been found for other viruses like HIV and Zika,” said senior author Zhe Han.
Last year, Han and his team identified the most toxic SARS-CoV-2 proteins in studies using fruit flies and human cells. They found a drug ‘selinexor’ reduced the toxicity of one of these proteins, but not the other one, known as Nsp6, according to the study.
In their latest study, they found that Nsp6, turned out to be the most toxic SARS-CoV-2 protein in the fly heart.
Next, the study said, they found that the Nsp6 protein hijacked the fruit fly’s cells in its heart to turn on the glycolysis process, which enables cells to burn the sugar glucose for energy. Typically, heart cells use fatty acids as an energy source, but switch over to sugar metabolism during heart failure as these cells to try to repair the damaged tissue.
The researchers also found the Nsp6 protein did added damage by disrupting the cell’s powerhouse, called the mitochondria, which produces energy from sugar metabolism, according to the study.
The team then blocked sugar metabolism in fruit flies and mouse heart cells using the drug 2-deoxy-D-glucose (2DG). They found that the drug reduced the heart and mitochondria damage caused by the Nsp6 viral protein, the study said.
“We know that some viruses hijack the infected animal’s cell machinery to change its metabolism to steal the cell’s energy source, so we suspect SARS-CoV-2 does something similar. The viruses can also use the byproducts of sugar metabolism as building blocks to make more viruses,” Han said.
“So, we predict this drug that changes the metabolism in the heart back to what it was before infection would be bad for the virus, by both cutting off its energy supply and eliminating the pieces it needs to replicate,” Han said.
The researchers said that fortunately 2DG is inexpensive and is used regularly in laboratory research. Although 2DG has not been approved by the U.S. Food and Drug Administration to treat disease, the drug is currently in clinical trials for treatment of Covid-19 in India, the study said.