Decoy receptor neutralizes coronavirus in cell cultures: Study

As the Covid-19 pandemic continues to spread, scientists are seeking ways to keep the coronavirus from infecting tissues once they’re exposed, now a new study suggests luring the virus with a decoy – an engineered, free-floating receptor protein – binds the disease and blocks infection.

To infect a human cell, a virus must first bind to a receptor protein on the surface of the cell, the study, published in the journal Science, said.

SARS-CoV-2, the coronavirus that causes Covid-19, binds to a receptor called ACE2, which plays a number of roles in regulating blood pressure, blood volume, and inflammation. It is found in tissues throughout the body, but especially in the lungs, heart, arteries, kidneys and intestines.

Many researchers hypothesize that the host of symptoms associated with COVID-19 may stem from the coronavirus binding to ACE2 and keeping it from doing its job.

“Administering a decoy based on ACE2 might not only neutralize infection, but may have the additional benefit of rescuing lost ACE2 activity and directly treating aspects of COVID-19,” said study researcher Erik Procko from the University of Illinois in the US.

As a potential therapeutic agent, a decoy receptor has one advantage over other drugs: To evade it, the virus would have to mutate in a way that would make it less infectious.

A benefit of a decoy receptor is that it closely resembles the natural receptor. Therefore, the virus cannot easily adapt to escape neutralization without simultaneously losing its ability to bind to its natural receptor, according to the researchers.

“This means the virus has limited ability to acquire resistance,” Procko said.

For the findings, the research team examined more than 2,000 ACE2 mutations and created cells with the mutant receptors on their surfaces.

By analysing how these interacted with the coronavirus, the study found a combination of three mutations that made a receptor that bound to the virus 50 times more strongly, making it a much more attractive target for the virus.

The research team then made a soluble version of the engineered receptor. Detached from cells, the soluble receptor is suspended in solution and free to interact with the virus as a decoy receptor.

“Researchers verified the strong affinity between the virus and the decoy receptor, rivalling the best antibodies identified to date,” Procko said.

“Furthermore, we found that the decoy receptor not only binds to the virus in live tissue cultures, it effectively neutralizes it, preventing cells from becoming infected,” Procko added.