SARS-CoV-2 infection causes COVID-19. The presence of the virus in the cardiac tissue of patients with COVID-19 suggests this is a direct, rather than secondary, the effect of infection. People infected with COVID-19 are at a significantly higher risk for developing heart muscle inflammation, abnormal heart rhythms, blood clots, stroke, heart attacks, and heart failure for at least a year after infection compared to those with not been infected with the virus.
However, scientists have rapidly developed vaccines and medications to lessen the severity of COVID-19 disease; these therapies do not protect the heart or other organs from damage.
Scientists at the University of Maryland School of Medicine’s (UMSOM) Center for Precision Disease Modeling identified how SARS-CoV-2 damages heart tissue.
Last year, in research involving fruit flies and human cells, the most lethal SARS-CoV-2 proteins were discovered. They found a promising drug selinexor reduced the toxicity of one of these proteins but not the other one, known as Nsp6.
In this study, scientists found that Nsp6 was the most toxic SARS-CoV-2 protein in the fly heart. They then discovered that the Nsp6 protein hijacked the fruit fly’s heart cells to activate the glycolysis process, allowing cells to burn the sugar glucose for energy. Heart cells typically use fatty acids as an energy source, but during heart failure, as these cells attempt to heal the damaged tissue, they convert to sugar metabolism. The scientists discovered that the Nsp6 protein disrupted the mitochondria, the powerhouse of the cell that uses sugar metabolism to make energy.
Later, using the drug 2-deoxy-D-glucose (2DG), scientists blocked sugar metabolism in fruit flies and mouse heart cells. They found that the drug reduced the heart and mitochondria damage caused by the Nsp6 viral protein.
Senior author Zhe Han, Ph.D., Professor of Medicine and Director of the Center for Precision Disease Modeling at UMSOM, 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. So, we predict this drug that changes the metabolism in the heart back to what it was before the infection would be bad for the virus by cutting off its energy supply and eliminating the pieces it needs to replicate.”
Scientists noted, “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 the treatment of COVID-19 in India.”
Mark T. Gladwin, MD, Vice President for Medical Affairs at the University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, UMSOM, said, “Too many Americans who have recovered from COVID wind up with dangerous heart conditions weeks or months later, and we need to learn the fundamental reasons for why this is happening. With this research elucidating the pathways of the Nsp6 protein, we can refine the treatments we target for future research with the ultimate aim of reversing further heart damage in these patients.”