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Researchers at the University of Maryland School of Medicine (UMSOM) found the most toxic protein produced by SARS-CoV-2 and then used an FDA-approved cancer drug to mitigate the lethal effects.
In their experiments in fruit flies and human cell lines, the team found the cell process that the virus hijacks. They discovered new potential candidate drugs that could be tested for treating severe Covid-19 disease patients.
Their findings were published in the journals Cell & Bioscience, a Springer Nature journal.
“Our work suggests there is a way to prevent SARS-COV-2 from injuring the body’s tissues and doing extensive damage,” says senior author of the study Zhe “Zion” Han, PhD, Associate Professor of Medicine and Director of the Center for Precision Disease Modeling at UMSOM.
He noted that the most effective drug against Covid-19, remdesivir, only prevents the virus from making more copies of itself. However, it does not protect already infected cells from damage caused by the viral proteins.
The authors of the study discovered that a viral protein, known as Orf6, was the most toxic killing about half of the human cells. Two other proteins (Nsp6 and Orf7a) also proved toxic, killing about 30-40 per cent of the human cells.
Dr. Han’s team found that the virus’s toxic Orf6 protein sticks to multiple human proteins that have the job of moving materials out of the cell’s nucleus--the place in the cell that holds the genome, or the instructions for life.
They then discovered that one of these human moving proteins, targeted by the virus, gets blocked by the cancer drug selinexor.
The researchers then tested selinexor on human cells and fruit flies making the toxic viral protein to see if the drug could help reverse the damage. Selinexor, like many cancer drugs, is itself toxic.
However, the drug improved human cell survival by about 12 per cent. Selinexor prevented early death in about 15 per cent of the flies making the toxic viral protein. Selinexor is FDA-approved to treat certain blood cancers.
“More than 1,000 FDA-approved drugs are in clinical trials to test as treatments for Covid-19, and luckily a trial testing selinexor, the drug used in our study, is being performed already,” said Dr. Han.
“If this trial proves to be successful, our data will have demonstrated the underlying mechanism for why the drug works,” he added.
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