Detrimental effects of the most toxic proteins made by SARS-COV-2, the virus that causes COVID-19 are shown to be blunt by an FDA-approved cancer drug.
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‘Detrimental effects of the most toxic proteins made by SARS-COV-2, the virus that causes COVID-19 are shown to be blunt by an FDA-approved cancer drug – selinexor. The drug improved human cell survival by about 12% and also prevented cellular damage caused by the virus. This illuminates the new potential candidate drugs that could be tested for treating severe COVID-19 disease patients.’
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"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, Ph.D., Associate Professor of Medicine and Director of the Center for Precision Disease Modeling at UMSOM. ![twitter](https://images.medindia.net/icons/news/social/twitter.png)
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The author notes that remdesivir, the most effective drug against Covid-19 prevents the virus only from making more copies of it, but the damage caused by the viral proteins is not protected in the already infected cells.
Hijack Mechanism of COVID-19
SARS-COV-2 virus infects the cells and hijacks them into making proteins from each of its 27 genes. The study team introduced each of these 27 SARS-CoV-2 genes in human cells to examine their toxicity. 12 fruit fly lines were also generated to express SARS-CoV-2 proteins that may cause toxicity based on their structure and predicted function.
It was found that a viral protein, known as Orf6, was the most toxic that kills about half of the human cells. The 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).
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Problems like fewer branches in their lungs or fewer energy-generating power factories in their muscle cells were seen in those fruit flies that lived.
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The team also discovered that the cancer drug – selinexor is capable of blocking one of these human moving proteins, targeted by the virus after testing the drug on human cells and fruit flies. The drug was capable of reversing the cellular damage.
Selinexor is FDA-approved to treat certain blood cancers. Like many cancer drugs, selinexor is itself toxic. But, after accounting for its toxic effects, the drug improved human cell survival by about 12%.
It also prevented early death in about 15% of the flies that made the toxic viral protein. Branches in the lungs and the energy-generators in the muscle cells were also shown to be restored by the drug.
"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. If this trial proves to be successful, our data will have demonstrated the underlying mechanism for why the drug works", says Dr. Han.
Source-Medindia