Engineered Decoy ACE2 Receptors That Neutralize Coronavirus and Block Infection Could Directly Treat COVID-19

To infect a human cell, a virus must first bind to a receptor protein on the surface of the cell. 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.

Although ACE2 binds to SARS-CoV-2, it is not optimized for that purpose, which means that subtle mutations to the receptor could make it bind more strongly, thus making it an ideal candidate for a decoy receptor. The researchers examined more than 2,000 ACE2 mutations and created cells with the mutant receptors on their surfaces. By analyzing how these interacted with the coronavirus, they 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 researchers then went on to make 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.

The researchers have verified the strong affinity between the virus and the decoy receptor, rivaling the best antibodies identified to date. Furthermore, they found that the decoy receptor not only binds to the virus in live tissue cultures, it effectively neutralizes it, preventing cells from becoming infected. Further work is required to determine whether the decoy receptors could be an effective treatment of or preventive agent against COVID-19.

“Administering a decoy based on ACE2 might not only neutralize infection, but also may have the additional benefit of rescuing lost ACE2 activity and directly treating aspects of COVID-19,” said Erik Procko, a professor of biochemistry at the University of Illinois, Urbana-Champaign, who led the study. “Administering a decoy based on ACE2 might not only neutralize infection, but also may have the additional benefit of rescuing lost ACE2 activity and directly treating aspects of COVID-19.”

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University of Illinois at Urbana-Champaign