Researchers detected endogenous nano-bubbles carrying the ACE2 protein (evACE2) in the blood of COVID-19 patients and observed that these nano-sized particles may prevent infection by SARS-CoV-2 virus strains. The protein functions as a decoy in the body and might be used to produce a therapy for the prevention and treatment of existing and future SARS-CoV-2 strains, as well as future coronaviruses. It might be sprayed into the nose.
In preclinical studies, researchers from Northwestern Medicine and The University of Texas MD Anderson Cancer Center discovered natural nano-bubbles containing the ACE2 protein (evACE2) in the blood of COVID-19 patients, and found that these nano-sized particles can block infection from broad strains of SARS-CoV-2 virus.
The evACE2 functions as a decoy in the body and might be used as a therapy for the prevention and treatment of existing and future SARS-CoV-2 strains, as well as future coronaviruses, according to the researchers. Once established as a therapeutic substance, it may be used as a biological therapy for humans with low side effects.
The research is the first to demonstrate that evACE2 proteins can combat novel SARS-CoV-2 variants with the same or higher efficiency than inhibiting the original strain. These evACE2 micro bubbles were discovered in human blood as a natural anti-viral reaction, according to the researchers. The greater the amounts of evACE2 discovered in the patient’s blood, the more serious the condition.
The study will be published in the journal Nature Communications on January 20.
Dr. Huiping Liu, an associate professor of pharmacology and medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician, said, “Whenever a new mutant strain of SARS-CoV-2 emerges, the original vaccine and therapeutic antibodies may lose power against alpha, beta, delta, and the most recent omicron variants.” “However, the beauty of evACE2 is its ability to prevent wide strains of coronaviruses from infecting people, including the present SARS-CoV-2 and even future SARS coronaviruses.”
“When administered to the airway through droplets, our mice trials reveal the therapeutic potential of evACE2 in preventing or inhibiting SARS-CoV-2 infection,” Liu added.
The evACE2 proteins are nanoparticle-sized lipid (fat) bubbles that express the ACE2 protein, acting as grips for the virus to grasp. The SARS-CoV-2 virus is lured away from the ACE2 protein on cells by these bubbles, which is how the virus infects cells. Instead of cellular ACE2, the viral spike protein grips the handle of evACE2, stopping it from entering the cell. The virus will either float about harmlessly or be removed by a macrophage immune cell after it has been trapped. It can no longer induce infection at that moment.
Dr. Raghu Kalluri, chair of cancer biology at MD Anderson, said, “The key takeaway from this study is the identification of naturally occurring extracellular vesicles in the body that express the ACE2 receptor on their surface and serve as part of the normal adaptive defense against COVID-19-causing viruses.” “Based on this, we’ve identified a method to use this natural resistance as a new possible therapeutic for this deadly infection.”
A continually evolving virus, SARS-CoV-2, has expanded and challenged the COVID-19 epidemic. The changing target of pathogenic coronavirus, which continually changes into new virus strains (variants) with mutations, is one of the most difficult difficulties. Due to vaccine inefficiencies and resistance to therapeutic monoclonal antibodies, these novel viral strains have diverse alterations in the viral spike protein, resulting in high infection rates and greater breakthroughs.
“It’s still critical to find new therapies,” Liu added. “We believe evACE2 will be able to meet the challenges and fight broad strains of SARS-CoV-2 and future emerging coronaviruses to protect the immunocompromised (at least 2.7 percent of U.S. adults), unvaccinated (94 percent in low-income countries and more than 30 percent in the United States), and even vaccinated from breakthrough infections.”
A patent on evACE2 has been filed by Northwestern University and MD Anderson Cancer Center. The objective is to work with business partners to create evACE2 as a biological therapeutic solution for COVID-19 prevention and treatment (nasal spray or injectable therapies). Exomira, a startup business founded by Liu and another co-senior author, Deyu Fang of Northwestern’s pathology department, will take this patent and develop evACE2 as a treatment.
This work was co-authored by a group of more than 30 people. Lamiaa El-Shennawy, Andrew Hoffmann, and Nurmaa Dashzeveg, all of the Liu lab at Northwestern, and Kathleen McAndrews, of MD Anderson’s Raghu Kalluri lab, are among the four main co-first authors. Drs. Michael Ison (infectious diseases), Yuan Luo (preventive medicine), Alexis Demonbreun (pharmacology), and Daniel Batle (nephrology and hypertension) of Northwestern University, as well as Drs. Dominique Missiakas and Glenn Randall of the University of Chicago Howard T. Ricketts Laboratory and Tujin Shi of the Pacific Northwest National Laboratory, all contributed significant work to the publication.
Valerie LeBleu, an MD/MBA student at Feinberg and Kellogg School of Management and previously an associate professor of cancer biology at MD Anderson, facilitated the connection between Northwestern and M.D. Anderson.
The Chicago Biomedical Consortium Accelerator Award, the Northwestern University Feinberg School of Medicine Emerging and Re-emerging Pathogens Program, the National Cancer Institute, the Blood Biobank fund, and Lyda Hill Philanthropies all contributed to the project, as did Northwestern’s pharmacology and pathology departments, Northwestern University Clinical and Translational Sciences Institute, and the Robert H. Lurie Comprehensive Cancer Center.
