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A new study published in the journal Nature Communications suggested that prodrug GC376 which is used to treat coronavirus disease in feline can be effective against the widespread novel coronavirus.
Prodrugs are compounds that have to be metabolized inside the body before they become active. GC376 gets converted to GC373.
A group of researchers at the University of Alberta, Canada, noted in the study that the prodrug targets an enzyme called Mpro in the SARS-CoV-2 and is a strong drug candidate for the treatment of coronavirus disease since it is already shown to be effective in animals.
The research team is set to launch phase 1 clinical trials of the drug soon.
Feline coronavirus
Feline coronavirus FCoV is a common infection that infects around 25 to 40 per cent of domestic cats in the world.
The virus enters a cat’s body through the oral route (licking, for example) and multiplies in the intestines. The cat will expel the virus in its feces where the virus may survive for up to a few weeks. Disinfectants can quickly destroy the FCoV.
According to the study, most cats that get this infection are asymptomatic. However, they may develop a mild form of diarrhea or it could lead to a life-threatening condition called feline infectious peritonitis (FIP).
The latter only develops when the FCoV virus develops a mutant strain inside the intestinal tract of the cat that can infect macrophages (a type of immune system cell) and spread throughout the body.
Prodrug GC376
Mpro is a protease present in the SARS-CoV-2 virus that helps the virus replicate and make copies of itself.
Prodrug GC376 has been proposed to have broad specificity against the Mpro of the novel coronavirus previously. To study the effect of this drug against the SARS-CoV-2 virus, the researchers exposed the virus to the drug in cell cultures.
It was found that GC376 when incubated with SARS-CoV-2 converts to GC373, which binds to the active site of Mpro protease, inhibiting the function of the protease. The active site of an enzyme is a pocket in the enzyme wherein the substrate (the compound an enzyme acts on) binds to it.
“We determined the three-dimensional shape of the protease with the drug in the active site pocket, showing the mechanism of inhibition. This will allow us to develop even more effective drugs," said Joanne Lemieux, the corresponding author of the study and a professor of biochemistry at the University of Alberta, Canada, as per the news release by the university.
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