Novel Coronavirus too cunning? Scientists are developing an effective decoy that neutralizes viruses and prevents cell infections

With the novel Coronavirus pandemic, scientists hope to find more effective ways to prevent the novel Coronavirus from infecting the tissue it has released, thereby “cutting off” transmission from source.
A new study suggests that it is possible to “trap” a virus with a decoy and prevent infection.

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The decoy is a designed, free-floating receptor protein.
Erik Procko, a professor of biochemistry at the University of Illinois at Urbana-Champaign, led the study, which was published in the journal Science.

Scientists are developing effective decoys

To infect human cells, the virus must first bind to receptor proteins on the cell surface.
Novel Coronavirus develops an infection by binding to a receptor called ACE2.
ACE2 plays a number of roles in regulating blood pressure, blood volume, and inflammation — it exists in tissues throughout the body, particularly in the lungs, heart, arteries, kidneys, and intestines.
Many researchers have speculated that the high number of symptoms associated with COVID-19 may be due to novel Coronavirus combining with ACE2, so preventing it from acting is a critical step.

“The use of ace2-based soluble decoys may not only neutralize infection, but may also have the additional benefit of saving lost ACE2 activity for direct treatment of COVID-19.”
Professor Erik Procko says.

As a potential therapeutic agent, the trap receptor has one advantage over other drugs: in order to evade the trap receptor, the virus must mutate to make it less infectious.

“One of the nice things about bait receptors is that they are very similar to natural receptors.
As a result, viruses cannot easily adapt to escape neutralization without losing their binding to natural receptors.
That means the ability of the virus to acquire resistance is limited.”
“Although ACE2 binds to SARS-COV-2, it is not optimized for this purpose, meaning that small mutations in the receptor may make it bind more strongly,” Erik Procko said.
This makes it an ideal candidate for a decoy receptor.”

Procko examined more than 2,000 ACE2 mutations and created cells with mutant receptors on their surfaces.
By analysing how these genes interact with the coronavirus, he found that a combination of three mutations made the receptor bind to the virus 50 times stronger, making it a more attractive target for the virus.

Novel Coronavirus decoys

Figure: Sequence preference of ACE2 residues with high S binding in SARS-COV-2.

Procko then makes a soluble engineered receptor.
The soluble receptor is suspended in solution after separation from the cell and interacts with the virus as a decoy receptor.

After Procko posted his findings to a preprint server, a colleague connected him to the U.S. Army Institute of Infectious Disease Medicine.
The researchers there, along with the laboratory of David Kranz, a professor of biochemistry at Illinois, demonstrated a strong affinity between the virus and the deception-stronger than the best antibodies identified so far.
In addition, they found that the trap receptor not only binds to the virus in living tissue culture, but also effectively neutralizes the virus and prevents cells from becoming infected.

However, further research is needed to see whether these trap receptors can be effective treatment or prevention agents for COVID-19.
“We are testing the bait receptor in mice to see if it is safe and stable, and if it is successful, we hope to demonstrate its treatment of disease in animals and hopefully this data will lead to clinical trials.”
Professor Erik Procko is also currently exploring how the trap receptor binds to other coronaviruses that could become future pandemics if they spread from bats to humans.

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