Researchers design and test protein that may lead to COVID-19 therapeutic

A novel receptor protein that binds to the SARS-CoV-2 virus and prevents it from entering cells may hold promise for treating COVID-19 and other coronavirus-related diseases, according to research published online Aug. 4 in the journal SCIENCE.

As scientists race to find treatments for COVID-19, many are focused on a specific protein called angiotensin-converting enzyme 2, or ACE2, which is found on various cell surfaces throughout the human body. Its purpose is to generate smaller proteins that regulate functions within the cell. Using the spike-like protein on its surface, the SARS-CoV-2 virus binds to ACE2 prior to entry and infection of cells. Thus, ACE2 acts as a receptor for the virus that causes COVID-19.

In the study, Dr. Erik Procko and scientists at the University of Illinois engineered a novel receptor that resembles ACE2, with the intent of using it as a "decoy" that can bind to the virus before it can latch onto ACE2 at the cell surface and invade the cell. First, Procko 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 spike protein, he found a combination of three mutations that made a receptor that bound to the virus more strongly and made it a more "attractive" target for the virus.

After Procko posted his findings to a preprint server, a colleague connected him with the U.S. Army Medical Research Institute of Infectious Diseases. USAMRIID scientists, including Dr. Andrew Herbert of The Geneva Foundation, agreed to test the receptor in cells using live SARS-CoV-2.

"We were already in the process of testing several therapeutic candidates for SARS-CoV-2, and Erik's approach seemed novel--and certainly compelling enough to give it a shot," commented Herbert.