New Delhi: Scientists in the US have developed a new drug that can turn SARS-CoV-2 against itself and prevent the deadly virus from infecting people.
The Scripps Research Institute researchers believe the drug, called NMT5, is likely effective against the 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 attaches to to infect cells.
When the virus is nearby, its path into human cells is blocked via the ACE2 receptor. However, in the absence of the virus, ACE2 can function as usual, the researchers said.
“The great thing about this drug is that we actually turn the virus against itself,” said study leader Stuart Lipton, a professor at the Scripps Research Institute.
The team tested a library of compounds and identified NMT5 with two key properties: it could recognize and bind to a pore on the surface of SARS-CoV-2 and chemically modify human ACE2 using a nitroglycerin fragment as a warhead.
The researchers realized that this could turn the virus into a vehicle for its own demise.
They characterized and tested NMT5 in both isolated cells and animals. The study showed how NMT5 tightly binds 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 when it gets close enough. When the virus gets close to ACE2 to infect a cell, it means that NMT5 adds a “nitro group” to the receptor.
When ACE2 is modified in this way, its structure changes temporarily – for about 12 hours – so that the SARS-CoV-2 virus can no longer attach to it and cause infection.
“What’s really nice is that this only affects the availability of ACE2 locally if the virus attacks it. It doesn’t shut down all of the function of ACE2 elsewhere in the body, which allows this protein to function normally,” Lipton said.
In cell culture experiments testing how well the Omicron variant of SARS-CoV-2 can bind to human ACE2 receptors, the drug prevented 95 percent of viral binding.
In hamsters with COVID-19, NMT5 reduced virus levels by 100-fold, cleared blood vessel damage in the animals’ lungs and reduced inflammation, the 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 blocking part of a virus directly, which can force it to develop resistance to the drug.
Because NMT5 only uses the virus as a carrier, researchers believe the drug is likely effective against many other variants of SARS-CoV-2.
“We expect this compound to remain effective even as new variants emerge because it doesn’t rely on attacking parts of the virus that mutate frequently,” said Chang-ki Oh, the study’s lead scientist and first author.
Although the researchers have only studied the compound in animal models, they are now making a version of the drug to evaluate for human use while conducting additional safety and efficacy studies in animals.
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