Scientists in the US have developed a new drug that can turn SARS-CoV-2 against itself and stop the deadly virus from infecting humans.
Researchers at The Scripps Research Institute believe that the drug, called NMT5, has the potential to be effective against emerging forms. SARS-CoV-2,
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medicine described in the journal Nature Chemical BiologyCoats SARS-CoV-2 with chemicals that can temporarily replace the human ACE2 receptor – the molecule that the virus normally carries to infect cells.
When the virus is in close proximity, its passage through the ACE2 receptor into human cells is blocked. In the absence of the virus, however, ACE2 can function as usual, the researchers said.
“What’s so clear about this drug is that we’re actually turning the virus against itself,” said senior author Stuart Lipton, a professor at The Scripps Research Institute.
The team tested a library of compounds and pinpointed NMT5 as having two key properties: it can recognize and attach to a pore on the surface of SARS-CoV-2, and chemically binds to human ACE2 with nitroglycerin. Can be modified as a warhead by using a piece of K.
The researchers realized that this could turn the virus into a delivery vehicle for its own demise.
They characterized and tested NMT5 in individual cells as well as in animals. Study reveals how NMT5 strongly binds to SARS-CoV-2 Viral particles such as viruses move through the body.
The researchers then uncovered details of how the drug would add a chemical similar to nitroglycerin to certain molecules if it got close enough. When the virus approaches ACE2 to infect a cell, it converts to NMT5 by adding a “nitro group” to the receptor. When ACE2 is modified in this way, its structure is temporarily altered – for about 12 hours – so that the SARS-CoV-2 virus can no longer bind to it to cause infection. “What is really beautiful is that it only reduces the availability of ACE2 locally when the virus is coming at it. It does not reduce all of the functions of ACE2 elsewhere in the body, allowing for normal function of this protein,” Lipton said.
In cell culture experiments that tested how well the Omicron version of SARS-CoV-2 could bind to human ACE2 receptors, the drug prevented 95 percent of viral binding.
The researchers said that in hamsters with COVID-19, NMT5 reduced virus levels by 100-fold, eliminated blood vessel damage in the animals’ lungs, and reduced inflammation.
He said the drug also showed effectiveness against about a dozen other types of the virus, including alpha, beta, gamma and delta strains.
Most anti-viral drugs work by directly blocking the part of the virus that may be pressing on it to develop resistance to the drug.
Since NMT5 is only using the virus as a carrier, the researchers believe the drug has the potential to be effective against many other variants. SARS-CoV-2,
Chang-Ki Oh, a senior staff scientist and first author of the research, said, “We expect this compound to remain effective even when new forms are exposed, as it does not rely on attacking the parts of the virus that do not. are usually mutated.” ,
Although researchers have only studied the compound in animal models, they are now building a version of the drug for evaluation of human use while conducting additional safety and effectiveness tests in animals.
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