As covid-19 continues to evolve in the United States, researchers are now developing the next generation of therapies, including a new approach that could help reduce the time it takes to recover from the disease.
While existing treatments include antivirals, antibody, and steroids, scientists in the United States and Europe are now focusing on decoying the receptors to which the virus normally binds, potentially neutralizing its harmful effects.
To develop the new therapy, scientists first had to design mice with a variant of the human protein known as angiotensin-converting enzyme 2, or ACE2. This resides on the surface of cells and helps regulate phenomena such as scarring, inflammation and blood pressure.
While ACE2 receptors can be found on cells all over the body, they are especially prevalent in the lungs, heart, kidneys, and liver, the disease organs. usually attacks.
To protect real ACE2 receivers, here’s how the decoy does its job:
Usually, the spike proteins on the surface of the virus act as keys for the ACE2 receptors, opening the door to infection. But the decoys, administered intravenously or through the nose depending on the stage of the disease, intercept the spike protein, pulling it away from the true receptors. After infection, treatment could lower the viral load inside the body, which could mean faster recovery times for patients.
In a study led by Daniel Batlle, a professor of medicine at Northwestern University, the mice infected with the disease and given the treatment showed only mild symptoms compared to the untreated animals, which died.
Batlle’s team began work on decoy proteins in January 2020 after learning about the first US case, building on knowledge gained during the 2003 SARS-CoV outbreak in China.
“We knew that the receptor for SARS-CoV-2 would be very likely to be ACE2, as it had already been shown to be the case for SARS-CoV,” Batlle said.
But applying this knowledge was not that simple. Michael jewett, a chemical engineering professor at Northwestern University who was not involved in the study, likens the complex process of making a decoy to a particularly devilish puzzle.
“Reengineering complex biological systems can be tricky,” says Jewett. “It’s a bit like solving a puzzle and every time you put a piece, the rest of the puzzle changes.”
Jewett also says that compared to antibody treatments, decoys should be cheaper and easier to use. And some experts are optimistic about the decoy’s ability to ward off both the original viral strain and future mutations.
In another study, using a process called deep mutational scanning, Erik Procko, a professor of biochemistry at the University of Illinois Urbana-Champaign, was able to visualize thousands of different ACE2 mutations in a single experiment and see which ones might better attract and bind to the virus. Then his team built decoys that mimicked the ones that worked best. The decoys do not attach to cells but float in the fluid between them to catch the virus before it binds to the true ACE2 receptors.
Using a combination of three mutations, his team were able to dramatically increase the decoy’s affinity for covid-19. They created decoy receptors that bound to the virus 50 times more strongly than ACE2.
To test the approach, Procko’s team used tissue from mice instead of live animals. “In in vitro tissue culture, we know that some of the decoy receptors are just as potent – sometimes a bit better, sometimes a bit less, but overall just as potent – as the monoclonal antibodies that have emergency use clearance or are in testing, ”says Procko.
One of the concerns was that one of these mutations could allow a so-called viral breakout and help build the virus’s resistance to treatment. But because the decoys closely resemble natural receptors, Procko says, the virus is not likely to evolve abnormally due to their action.
Due to differences in infrastructure and education, access to synthetic biology technologies is unevenly distributed around the world. More research and more funding is needed before such therapy becomes available to the public. But advancements like these could eventually help create inexpensive, portable, and easy-to-use treatments for the disease.
“There are promising signs that decoys that closely resemble the human ACE2 receptor will be potent and effective against all of these newer variants,” Procko said. “I wouldn’t be surprised if some of these new generation decoys hit the clinic within a few years. “