Can you spot fake receptors? Neither can the coronavirus.


As covid-19 continues to evolve in the United States, researchers are now developing next-generation therapies, including a new method that can help reduce the time it takes to recover from the disease.

Although current treatments include anti-viral drug, Antibody, with Steroid, Scientists in the United States and Europe are now focusing on making baits for the receptors that viruses normally bind to, which may eliminate their harmful effects.

In order to develop this new therapy, scientists must first modify mice with a variant of a human protein called angiotensin-converting enzyme 2 or ACE2. It is located on the surface of cells and helps to regulate phenomena such as healing, inflammation and blood pressure.

Although ACE2 receptors can be found in cells throughout the body, they are especially common in organs with diseases such as the lung, heart, kidney, and liver Usually attacked.

In order to protect the real ACE2 receptor, the decoy works as follows:

Usually, the spike protein on the surface of the virus is like the key to the ACE2 receptor, opening the door to infection. However, depending on the stage of the disease, bait administered intravenously or through the nose will intercept the spike protein and keep it away from the real receptor. After infection, treatment can reduce the viral load in the body, which may mean faster recovery time for the patient.

In one by Daniel BattelleThe professor of medicine at Northwestern University said that compared with animals that died without treatment, mice infected with the disease and treated had only mild symptoms.

As of today, there is only one clinical Trial ACE2 products have been completed in patients with moderate to severe symptoms. Even so, more and more researchers support this new therapy.

After learning about the first case in the United States, Batlle’s team began to study the bait protein in January 2020, based on the knowledge gathered from the 2003 SARS-CoV outbreak in China.

“We know that the receptor for SARS-CoV-2 is likely to be ACE2, because it has been proven that this is the case with SARS-CoV,” Butler said.

But applying this knowledge is not so simple. Michael JuvetThe professor of chemical engineering at Northwestern University who was not involved in the research compared the complex process of making bait to a particularly terrifying puzzle.

“Redesigning complex biological systems can be tricky,” Jewett said. “It’s a bit like solving a puzzle. Every time you put a piece in, the rest of the puzzle will change.”

Jewett also said that bait should be cheaper and easier to use than antibody therapy. Some experts are optimistic about the bait’s ability to resist the original virus strain and future mutations.

In another study, Using a process called deep mutation scanning, Eric Procco A professor of biochemistry at the University of Illinois at Urbana-Champaign was able to look at thousands of different ACE2 mutations in a single experiment to see which ones can better attract and bind viruses. Then his team built baits that mimic the best-performing bait. The bait does not attach to the cells, but floats in the fluid between the cells to capture the virus before it binds to the real ACE2 receptor.

By using a combination of three mutations, his team was able to significantly increase the affinity of the bait for covid-19. The binding strength of the bait receptor they created to the virus is 50 times that of ACE2.

To test the method, Procko’s team used mouse tissue instead of live animals. “In in vitro tissue culture, we know that some decoy receptors are as effective as monoclonal antibodies that have been authorized for emergency use or clinical trials — sometimes better, sometimes worse, but generally just as effective. Trials,” Procco said .

One concern is that one of these mutations may allow the so-called virus to escape and help strengthen the virus’s resistance to treatment. But because baits are very similar to natural receptors, Procco said that viruses are unlikely to evolve because of their effects.

Due to differences in infrastructure and education, access to synthetic biology technology is unevenly distributed around the world. Before this therapy becomes publicly available, more research and more funding are needed. But advances like this may ultimately help create low-cost, portable, and easy-to-use disease treatments.

“There are promising signs that decoys that are very similar to the human ACE2 receptor are effective for all these new variants,” Procco said. “If we have some next-generation bait reaching the clinic within a few years, I wouldn’t be surprised.”


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