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As covid-19 continues to evolve in the US, researchers are currently developing a new generation of therapies, including a new approach that could help shorten the time it takes to recover from the disease.
While existing treatments include antiviral drugs, antibodies and steroids, scientists in the US and Europe are now focusing on trapping the receptors the virus normally binds to, potentially neutralizing its harmful effects.
To develop a new therapy, the scientists first had to design mice with a variant of the human protein known as angiotensin converting enzyme 2, or ACE2. It sits on the surface of cells and helps regulate phenomena such as healing, inflammation, and blood pressure.
Although ACE2 receptors can be found in cells throughout the body, they are especially prevalent in the lungs, heart, kidneys, and liver – organs that commonly affect disease.
To protect the true ACE2 receptors, the bait does its job as follows:
Typically, spike proteins on the surface of the virus act as clues to the ACE2 receptors, opening the path of infection. But baits, administered intravenously or through the nose, depending on the stage of the disease, intercept the spike protein, taking it away from the real receptors. Once infected, treatment can lower the viral load in the body, which could mean faster recovery for patients.
In one study by Daniel Butll, a professor of medicine at Northwestern University, mice that were infected with the disease and received treatment had only mild symptoms compared to animals that were not treated and that died.
To date, only one clinical trial of ACE2 has been completed in patients with moderate to severe symptoms. However, more and more researchers are supporting the new therapeutic agent.
Battle’s team began work on trap proteins in January 2020 after learning of the first case in the United States based on knowledge gleaned from the 2003 SARS-CoV outbreak in China.
“We knew it was very likely that ACE2 would be the receptor for SARS-CoV-2, as it had previously been shown to be the case for SARS-CoV,” says Butle.
But it was not so easy to apply this knowledge. Michael Jewett, a professor of chemical engineering at Northwestern University who was not involved in the study, compares the complex process of decorating with a particularly diabolical puzzle.
“Reengineering complex biological systems can be tricky,” says Jewett. “It’s like solving a puzzle, and every time you insert one piece, the rest of the puzzle changes.”
Jewett also says that baits should be cheaper and easier to use compared to antibody treatments. And some experts are optimistic about the decoy’s ability to ward off both the original virus strain and upcoming mutations.
In another study, using a process called deep mutation scanning, Eric Procco, professor of biochemistry at the University of Illinois at Urbana-Champaign, was able to look at thousands of different ACE2 mutations in one experiment and see which ones might best attract and bind to the virus. Then his team built lures that mimic the most effective ones. Traps do not attach to cells, but float in the fluid between them to catch the virus before it binds to the actual ACE2 receptors.
Using a combination of three mutations, his team was able to significantly increase the bait’s affinity for covid-19. They created decoy receptors that bind to the virus 50 times more strongly than ACE2.
To test this approach, Prokko’s team used mouse tissue instead of live animals. “In in vitro tissue culture, we know that some of the decoy receptors are just as effective – sometimes slightly better, sometimes slightly less, but generally just as effective – as monoclonal antibodies that are approved for emergency use or are in clinical use. practice. trials, ”says Prokko.
One problem was that one of these mutations could allow the so-called “escape” of the virus and help strengthen the virus’s resistance to treatment. But because baits are very similar to natural receptors, Procco says, the virus is unlikely to develop unnaturally as a result of their action.
Due to differences in infrastructure and education, access to synthetic biology technologies is unevenly distributed throughout the world. More research and more funding are needed before such therapy becomes generally available. But such advances may ultimately help create affordable, portable, and easy-to-use treatments for the disease.
“There are promising signs that baits very similar to the human ACE2 receptor will be effective and effective against all of these new variants,” says Prokko. “I wouldn’t be surprised if we have some of these next generation lures in a couple of years.”
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