New Delhi: US scientists have developed a new drug that can turn SARS-CoV-2 against itself and prevent death virus to infect humans.
Researchers at the Scripps Research Institute believe the drug, called NMT5, is likely to be effective against emerging variants of SARS-CoV-2.
The drug, described in the journal Nature Chemical Biology, coats SARS-CoV-2 with chemicals that can temporarily alter the human ACE2 receptor – the molecule the virus normally latches onto to infect cells.
When the virus is near, its way into human cells via the ACE2 receptor is blocked. In the absence of the virus, however, ACE2 can function as usual, the researchers said.
“What’s so interesting about this drug is that we turn the virus against itself,” said the study’s lead author, Stuart Lipton, a professor at the Scripps Research Institute.
The team tested a library of compounds and identified NMT5 as having two key properties: it could recognize and attach to a pore on the surface of SARS-CoV-2, and chemically modify human ACE2 using a fragment of nitroglycerin as warhead.
Researchers realized this could turn the virus into a delivery vehicle for its own demise.
They characterized and tested NMT5 in isolated cells as well as in animals. The study showed how NMT5 attaches tightly to SARS-CoV-2 virus particles as the viruses move through the body.
The researchers then revealed the details of how the drug adds a chemical, similar to nitroglycerin, to certain molecules if it gets close enough. When the virus approaches ACE2 to infect a cell, this results in NMT5 adding a “nitro group” to the receptor.
When ACE2 is changed in this way, its structure shifts temporarily – for about 12 hours – so that the SARS-CoV-2 virus can no longer bind to it to cause infection.
“What’s really beautiful is that it only knocks down the availability of ACE2 locally when the virus approaches it. It doesn’t knock down all the functions of ACE2 elsewhere in the body, allowing the functioning normal of this protein,” Lipton said.
In cell culture experiments testing the ability of the Omicron variant of SARS-CoV-2 to bind to human ACE2 receptors, the drug prevented 95% of viral binding.
In hamsters with COVID-19, NMT5 reduced virus levels 100-fold, eliminated damage to blood vessels in the animals’ lungs, and improved inflammation, the researchers said.
The drug has also shown effectiveness 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 a part of a virus that can cause it to develop resistance to the drug.
Since NMT5 only uses the virus as a carrier, researchers believe the drug is likely to be effective against many other SARS-CoV-2 variants.
“We expect this compound to continue to be effective even as new variants emerge, because it does not rely on attacking parts of the virus that commonly mutate,” said Chang-ki Oh, lead scientist and first research author.
Although the researchers only studied the compound in animal models, they are now making a version of the drug to be evaluated for human use, while performing additional safety and efficacy trials in animals.
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