Bioengineered protein may prevent COVID infection and improve survival

A new ACE2 protein developed by researchers at Northwestern Medicine improved survival and prevented brain infection in mice infected with SARS-CoV-2 when administered intranasally, according to a recent study. bottom. It was published in the journal Life Science Alliance.

SARS-CoV-2, the virus that causes COVID-19, uses the angiotensin-converting enzyme 2 (ACE2) protein as its primary receptor to infect healthy cells. Since the discovery of this mechanism in early 2020, the use of soluble ACE2 protein to neutralize SAR-CoV-2 infection has been investigated as a novel therapeutic approach.

for the past three years, Daniel Battle, M.D.Earl, Del Greco, Levin Professor of Nephrology/Hypertension, bioengineered to develop a soluble ACE2 protein, first in human organoids and later in SARS-CoV-2-infected mice, for potential therapeutics to reduce infection. studying sex.

A soluble protein called ACE2 618-DDC-ABD blocks the spike of the SARS-CoV-2 virus before it binds to the ACE2 receptor, preventing SARS-CoV-2 from entering and infecting healthy cells. increase.

“Since the native ACE2 protein circulates in low amounts and cannot actually prevent the virus from attaching to the cell membrane receptor, the cell membrane ACE2 receptor is always preferred. However, providing a sufficient amount of the appropriate soluble ACE2 protein at the right time can prevent the virus from attaching to cell membrane receptors and entering the cell. This is what is known as the ‘decoy action’ of soluble ACE2,” Batlle said.

in the previous work It was published in the American Journal of Nephrology, battle team When mice inoculated with a lethal dose of SARS-CoV-2 virus were given both intranasal and intraperitoneal decoy proteins, the mice showed nearly 100% survival and were found to reduce lung damage. I was.

“Our proteins have the property of increasing the duration of action. We modified it further to make it more cohesive,” says Batlle.

In the current study, Batlle’s team tested this therapeutic approach by administering a decoy protein, comparing intranasal and intraperitoneal (by injection) administration to mice before and after SARS-COV-2 infection. studied the effectiveness of

Overall, the 5-day survival rate was 0% for untreated mice, 40% for mice given i.p. was 90%. Additionally, in intranasally administered mice, the researchers found no detectable viral presence in the brains of the mice, and reduced viral presence and pathology in the lungs.

“We expected a difference between intranasal and systemic administration, but nasal administration was better, but probably not as much as we observed,” said Batlle.

In the future, their protein will be developed into an antiviral nasal spray that patients and healthcare providers can use the moment they test positive for SARS-CoV-2 or after contact with an infected person. is ideal.

“This study shows that soluble ACE2 protein is most effective against the SARS-CoV-2 virus when administered by the intranasal route. We believe it could be a novel antiviral strategy when administered to certain patients, hospital healthcare workers who are constantly exposed to the virus, or people who have been recently infected.” Jan Wysocki, MD, PhD, Research Associate Professor medicine Co-author of the study in the Department of Kidney Disease and Hypertension.

Luise Hassler, former research scientist in the Department of Nephrology and Hypertension, was the lead author of the study. Jared Ahrendsen, MD, PhDan assistant professor of pathology in the Department of Neuropathology, was also a co-author.

This work was supported by National Institutes of Health grant 1R21 AI166940-01, a gift from the Joseph and Bessie Feinberg Foundation, and the Biomedical Education Program.