Health
New drug could turn Covid virus against itself, fight subspecies
US scientists have developed a new drug that could counter SARS-CoV-2 against itself and prevent the deadly virus from infecting humans.
Researchers at the Scripps Research Institute think the drug, called NMT5, is likely to be effective against the new subspecies. SARS-CoV-2.
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Drugs listed in journals nature chemical biology, coating SARS-CoV-2 with a chemical that can transiently alter the human ACE2 receptor. This is the molecule that viruses normally latch onto in order to infect cells.
When the virus approaches, it blocks its pathway to human cells through the ACE2 receptor. But in the absence of the virus, ACE2 can function normally, researchers say.
“The beauty of this drug is that it actually turns the virus against itself,” said Stuart Lipton, lead author of the study and a professor at the Scripps Research Institute.
The team tested a library of compounds and identified NMT5 as having two important properties. It can recognize and bind to pores on the surface of SARS-CoV-2 and chemically modify human ACE2 using fragments of nitroglycerin as warheads.
Researchers have realized that this could turn the virus into a vehicle for its own demise.
They characterized and tested NMT5 not only in animals, but also in isolated cells.This study showed how NMT5 adheres tightly SARS-CoV-2 Virus particles as the virus moves through the body.
The researchers then revealed details of how the drug adds a nitroglycerin-like chemical to a specific molecule if brought close enough. When he approaches ACE2 for the virus to infect cells, it is converted to NMT5, which adds a “nitro group” to the receptor. This modification of ACE2 causes a temporary change in its structure (about 12 hours) that prevents the SARS-CoV-2 virus from binding to it and causing infection. “What’s really cool is that when the virus gets close to his ACE2, locally he just reduces the availability of ACE2. It knocks down all the functions of his ACE2 elsewhere in the body.” It doesn’t do it, but it allows the protein to function normally,” Lipton said.
In cell culture experiments, Omicron A variant of SARS-CoV-2 was able to bind to the human ACE2 receptor and the drug prevented 95% of virus binding.
In COVID-19-infected hamsters, NMT5 reduced viral levels 100-fold, abolished vascular damage in the animal’s lungs, and ameliorated inflammation, researchers said.
The drug also showed efficacy against nearly a dozen other variants of the virus, including alpha, beta, gamma and delta strains, they said.
Most antiviral drugs work by directly blocking part of the virus, putting pressure on it to evolve resistance to the drug.
Because NMT5 only uses the virus as a carrier, researchers believe the drug is likely to be effective against many other subspecies. SARS-CoV-2.
“Because this compound doesn’t rely on attacking parts of the virus that commonly mutate, we expect it to remain effective as new variants emerge,” said a senior staff scientist at the study. said Chang-ki Oh, lead author of .
Although the researchers have only studied the compound in animal models, they are conducting additional safety and efficacy trials in animals while creating a version of the drug to evaluate for human use.
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