In their experiments on fruit flies and human cell lines, the team uncovered the cellular process hijacked by the virus, shedding light on potential new drug candidates that could be tested to treat patients with Covid-19 disease. serious.
“Our work suggests that there is a way to prevent SARS-COV-2 from injuring body tissue and causing significant damage,” University of Maryland researcher Zhe “Zion” Han said.
The researcher notes that the most effective drug against Covid-19, remdesivir, only prevents the virus from making more copies of itself, but it does not protect already infected cells from damage caused by viral proteins.
SARS-COV-2 infects cells and hijacks them to make proteins from each of its 27 genes.
For the study, published in the journal Cell & Bioscience, the team introduced each of these 27 SARS-CoV-2 genes into human cells and examined their toxicity. They also generated 12 fruit fly lines to express SARS-CoV-2 proteins that can cause toxicity based on their predicted structure and function.
The researchers found that a viral protein, known as Orf6, was the most toxic killing of about half of human cells.
For the remaining experiments, the researchers focused only on the most toxic viral protein, in order to determine which cellular process the virus was hijacking during infection.
The team found that the virus’s toxic Orf6 protein adheres to several human proteins that are tasked with moving material out of the cell nucleus – the place in the cell that contains the genome or instructions for life.
They then discovered that one of these moving human proteins, targeted by the virus, was blocked by the anti-cancer drug selinexor. Researchers tested selinexor in 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, after accounting for its toxic effects, the drug improved human cell survival by about 12%.