Nano-bubble evACE2 fights new variants as well as or better than the original virus strain.
- The drug can be supplied as a nasal spray
- Acts as a lure to catch viruses before it enters the cell
- ‘It is urgent to identify new therapies’
- EVACE2 occurs naturally in COVID-19 patients as part of the antiviral response
Researchers at Northwestern Medicine and the University of Texas MD Anderson Cancer Center have identified natural nano-bubbles containing the ACE2 protein (evACE2) in the blood of COVID-19 patients and discovered that these nano-sized particles can block infection from broad strains of SARS-CoV-2 virus in preclinical studies.
evACE2 acts as a bait in the body and can serve as a therapeutic agent to be developed for the prevention and treatment of current and future strains of SARS-CoV-2 and future coronavirus, the researchers said. Once developed as a therapeutic product, it can benefit humans as a biological treatment with minimal toxicity.
The study is the first to show that evACE2 proteins are able to fight the new SARS-CoV-2 variants with the same or better efficacy than blocking the original strain. The researchers found that these evACE2 nanobubbles exist in human blood as a natural antiviral reaction. The more severe the disease, the higher the levels of evACE2 detected in the patient’s blood.
The magazine is published in Nature communication today (January 20, 2022).
“As a new mutant strain of SARS-CoV-2 increases, the original vaccine and therapeutic antibodies may lose potency against alpha, beta, delta, and the latest omicron variants,” said co-senior author of the study, Dr. Huiping Liu, an associate. professor of pharmacology and medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “But the beauty of evACE2 is its superpower to block broad strains of coronavirus, including the current SARS-CoV-2 and even future SARS coronaviruses from infecting humans.”
“Our mouse studies show the therapeutic potential of evACE2 to prevent or block SARS-CoV-2 infection when delivered to the airways via drops,” Liu said.
The evACE2 proteins are tiny nanoparticle-sized lipid (fat) bubbles that express the ACE2 protein as handles that the virus can grab. These bubbles act as decoys to lure the SARS-CoV-2 virus away from the ACE2 protein onto cells, which is how the virus infects cells. The virus tip protein grips the handle on evACE2 instead of cellular ACE2, preventing it from entering the cell. Once caught, the virus will either float harmlessly around or be removed by a macrophage immune cell. At that point, it can no longer cause infection.
“The key to 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-induced viruses,” said co-senior author Dr. Raghu Kalluri, President of Cancer Biology at MD Anderson. “Based on this, we have discovered a way to exploit this natural defense as a new potential therapy against this destructive virus.”
The COVID-19 pandemic has been prolonged and challenged by a constantly changing virus SARS-CoV-2. One of the biggest challenges is the motile target of pathogenic coronavirus, which is constantly evolving into new virus strains (variants) with mutations. These new viral strains contain various changes in the viral spike protein with high infection rates and increased breakthroughs due to vaccine inefficiency and resistance to therapeutic monoclonal antibodies.
“It remains urgent to identify new therapeutic agents,” Liu said. “We believe that evACE2 can meet the challenges and fight broad strains of SARS-CoV-2 and future new coronaviruses to protect immunocompromised (at least 2.7% of adults in the US), 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 pending patent on evACE2. The goal is to collaborate with industry partners and develop evACE2 as a biological therapeutic product (nasal spray or injected therapeutics) for the prevention and treatment of COVID-19. Liu and another co-senior author, Deyu Fang from Northwestern Pathology, have formed a startup company, Exomira, to take this patent and develop evACE2 as a therapeutic agent.
Reference: “Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2” January 20, 2022, Nature communication.
DOI: 10.1038 / s41467-021-27893-2
A team of more than 30 authors collaborated on this work. They include four lead authors Lamiaa El-Shennawy, Andrew Hoffmann and Nurmaa Dashzeveg, all from the Liu Laboratory in Northwestern, and Kathleen McAndrews from Raghu Kalluri Lab from MD Anderson. Several senior co-authors contributed significant 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), Dr. Dominique Missiakas and Glenn Randall at University of Chicago Howard T. Ricketts Laboratory and Tujin Shi at Pacific Northwest National Laboratory.
The collaboration between Northwestern and MD Anderson was promoted by co-author Valerie LeBleu, an MD / MBA student at Feinberg and Kellogg School of Management and former 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; National Cancer Institute, Blood Biobank Fund; and Lyda Hill Philanthropies. Northwestern Pharmacology and Pathology Departments; Northwestern University Clinical and Translational Sciences Institute; and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University also helped fund the work.
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