Home Cellular science The evACE2 nano-bubble fights new variants as well or better than the original strain of the virus

The evACE2 nano-bubble fights new variants as well or better than the original strain of the virus

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Scientists from Northwestern Medicine and the University of Texas MD Anderson Cancer Center have identified naturally occurring nanobubbles containing the protein ACE2 (evACE2) in the blood of COVID-19 patients and found that these nanoparticles can block infection by large strains of SARS-CoV-2 Virus in preclinical studies.

evACE2 acts as a decoy in the body and may serve as therapeutics to be developed for the prevention and treatment of current and future strains of SARS-CoV-2 and future coronaviruses, the scientists said. Once developed as a therapeutic product, it can benefit humans as a biological treatment with minimal toxicities.

The study is the first to show that evACE2 proteins are able to fight new SARS-CoV-2 variants with equal or greater efficacy than blocking the original strain. The researchers found that these evACE2 nano-bubbles exist in human blood as a natural antiviral response. The more severe the disease, the higher the levels of evACE2 detected in the patient’s blood.

The article will be published in Nature Communication January 20.

“Each time a new mutant strain of SARS-CoV-2 arises, the original vaccine and therapeutic antibodies may lose potency against the alpha, beta, delta, and newer omicron variants,” said the co-lead author of the study, Dr. Huiping Liu, associate. professor of pharmacology and medicine at Northwestern University Feinberg School of Medicine and physician at Northwestern Medicine. “However, the beauty of evACE2 is its superpower to prevent broad strains of coronaviruses, including current SARS-CoV-2 and even future SARS coronaviruses, from infecting humans.”

“Our mouse studies demonstrate the therapeutic potential of evACE2 to prevent or block SARS-CoV-2 infection when delivered to the airways via droplets,” Liu said.

The evACE2 proteins are tiny nanoparticle-sized lipid (fat) bubbles that express the ACE2 protein, like handles that the virus can grab onto. These bubbles act as decoys to lure the SARS-CoV-2 virus away from the ACE2 protein on the cells, which is how the virus infects the cells. The viral spike protein grabs the handle of evACE2 instead of the cellular ACE2, preventing it from entering the cell. Once captured, the virus will float harmlessly or be cleared by a macrophage immune cell. At this point, it can no longer cause infection.

“The key takeaway from this study is the identification of natural extracellular vesicles in the body that express the ACE2 receptor on their surface and are part of the normal adaptive defense against the viruses that cause COVID-19,” said the co- lead author, Dr. Raghu Kalluri, Chair of Cancer Biology at MD Anderson. “Based on this, we have discovered a way to harness this natural defense as a potential new therapy against this devastating virus.”

The COVID-19 pandemic has been prolonged and challenged by an ever-evolving virus, SARS-CoV-2. One of the biggest challenges is the moving target of the pathogenic coronavirus which is constantly evolving into new virus strains (variants) with mutations. These new virus strains harbor various changes in the viral spike protein with high infection rates and increased breakthroughs due to vaccine ineffectiveness and resistance to therapeutic monoclonal antibodies.

“There remains an urgent need to identify new therapies,” Liu said. “We believe that evACE2 can meet the challenges and fight broad strains of SARS-CoV-2 and future emerging coronaviruses to protect the immunocompromised (at least 2.7% of US adults), unvaccinated (94% in low-income countries and more than 30% in the United States) and even vaccinated against breakthrough infections.

Northwestern and MD Anderson have a patent pending on evACE2. The goal is to collaborate with industrial partners and develop evACE2 as a biological therapeutic product (nasal spray or injected therapeutic) for the prevention and treatment of COVID-19. Liu and another co-lead author, Deyu Fang of Pathology at Northwestern, formed a startup, Exomira, to take that patent and develop evACE2 as a therapeutic.

A team of more than 30 authors collaborated on this work. They include four co-first lead authors Lamiaa El-Shennawy, Andrew Hoffmann and Nurmaa Dashzeveg, all from Northwestern’s Liu Lab, and Kathleen McAndrews from MD Anderson’s Raghu Kalluri Lab. Several co-lead authors contributed important work to the publication, including Northwestern colleagues Drs. Michael Ison (infectious diseases), Yuan Luo (preventive medicine), Alexis Demonbreun (pharmacology) and Daniel Batle (nephrology and hypertension), Drs. Dominique Missiakas and Glenn Randall of the Howard T. Ricketts Laboratory at the University of Chicago and Tujin Shi of the Pacific Northwest National Laboratory.

The collaboration between Northwestern and MD Anderson was encouraged by co-author Valerie LeBleu, an MD/MBA student at the Feinberg and Kellogg School of Management and formerly assistant professor of cancer biology at MD Anderson.

The work was supported by the Chicago Biomedical Consortium Accelerator Award; Northwestern University Feinberg School of Medicine Emerging and Re-emerging Pathogens Program; the National Cancer Institute, the Blood Biobank fund; and Lyda Hill Philanthropies. Northwestern’s departments of pharmacology and pathology; Northwestern University Institute for Clinical and Translational Sciences; and the Robert H. Lurie Comprehensive Cancer Center at Northwestern University also helped fund the work.

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Materials provided by Northwestern University. Original written by Marla Paul. Note: Content may be edited for style and length.