Researchers at the University of Illinois, Urbana-Champaign, led a study that reveals that by luring the SARS-CoV-2 virus with a decoy—an engineered, free-floating receptor protein—that bind the virus and blocks infection. Led by Erik Procko, a professor of biochemistry, their findings were recently published in peer-reviewed journal Science. After the study was verified by a team, including the U.S. Army Medical Research Institute of Infectious Diseases, the implications for this National Institutes of Health (NIH) supported, novel approach become more intriguing.
TrialSite attempts to breakdown this study for ease of consumption.
What is the key hypothesis behind this research?
Many researchers hypothesize that the host of symptoms associated with COVID-19 may originate from the SARS-CoV-2 virus binding to ACE2 and thus keeping it from doing its job. ACE2 is a receptor that plays a number of roles in regulating blood pressure, blood volume and inflammation. As it turns out SARS-CoV-2 binds to ACE2 to then infect people.
Therefore, Procko asks, what if there was a way to actually “administer a decoy based on ACE2”? Could this both A) neutralize infection from the pathogen and B) rescue lost ACE2 activity hence treating aspects of COVID-19, reports the University of Illinois News Bureau’s Liz Ahlberg Touchstone.
What is a key argument for this approach?
The University of Illinois, Urbana-Champaign researchers suggest that such a potential therapeutic agent, that is the decoy receptor, has an advantage over other drugs in that to evade this drug, SARS-CoV-2 would have to mutate in a way that would make it less infectious. Hence, the decoy can serve as a way to dilute the pathogen.
Procko suggests “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.”
How did Procko and team come to this realization?
The team studied over 2,000 ACE2 mutations and created cells with the mutant receptors on their surfaces. After analyses of these interactions with SARS-CoV-2, the researcher found that a combination of three mutations that made a receptor that bound to the virus 50 times more strongly, making it much more attractive target for the virus.
How did they test this?
Procko 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.
How were his findings verified?
Procko initially posted his results to a preprint server. Thereafter, a colleague connected the Illinois researcher with the U.S. Army Medical Research Institute of Infectious Diseases. Researchers there, along with the lab of Illinois biochemistry professor David Kranz, verified the strong affinity between the virus and the decoy receptor, rivaling the best antibodies to date.
Moreover, the team observed that the decoy not only binds to the virus in live tissue cultures, it also effectively neutralizes it, thus actually preventing the human cells from SARS-CoV-2 infection!
Now the team, led by Procko, will test “whether the decoy receptor is safe and stable in mice, and if successful, we then hope to show treatment of disease in animals. Hopefully that data can facilitate a clinical trial.” Additionally, Procko suggests other exploration including investigation whether the receptor bonds to other coronaviruses with potential to become future pandemics if they cross from bats to humans form example.
Erik Procko, a professor of biochemistry
Call to Action: Interested in connecting with Professor Procko? See his contact info.