Nano bubbles could treat, prevent current and future strains of SARS-
CoV-2
Nano-bubble evACE2 fights new variants as well as or better than original strain of virus

Date:
January 21, 2022
Source:
Northwestern University
Summary:
Scientists have identified natural nano-bubbles containing the ACE2
protein (evACE2) in the blood of COVID-19 patients and discovered
these nano-sized particles can block infection from broad strains
of SARS-CoV- 2 virus. The protein acts as a decoy in the body
and can serve as a therapeutic to be developed for prevention and
treatment for current and future strains of SARS-CoV-2 and future
coronaviruses. It could be delivered as a nasal spray.



FULL STORY ========================================================================== Scientists 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
these nano-sized particles can block infection from broad strains of
SARS-CoV-2 virus in preclinical studies.


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

The study is the first to show evACE2 proteins are capable of fighting the
new SARS-CoV-2 variants with an equal or better efficacy than blocking the original strain. The researchers found these evACE2 nano bubbles exist
in human blood as a natural anti-viral response. The more severe the
disease, the higher the levels of evACE2 detected in the patient's blood.

The paper will be published in Nature Communications Jan. 20.

"Whenever a new mutant strain of SARS-CoV-2 surges, the original
vaccine and therapeutic antibodies may lose power against alpha, beta,
delta and the most recent omicron variants," said study co-senior author
Dr. Huiping Liu, an associate professor of pharmacology and of medicine
at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. "However, the beauty of evACE2 is its superpower
in blocking broad strains of coronaviruses, including the current
SARS-CoV-2 and even future SARS coronaviruses from infecting humans."
"Our mouse studies demonstrate the therapeutic potential of evACE2 in preventing or blocking SARS-CoV-2 infection when it is delivered to the
airway via droplets," Liu said.



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

"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," said co-senior author Dr. Raghu
Kalluri, chair of cancer biology at MD Anderson. "Building upon this,
we've discovered a way to harness this natural defense as a new potential therapy against this devastating virus." The COVID-19 pandemic has been extended and challenged by a constantly changing virus SARS-CoV-2. One of
the biggest challenges is the moving target of pathogenic coronavirus that constantly evolves into new virus strains (variants) with mutations. These
new viral strains harbor various changes in the viral spike protein
with high infection rates and increased breakthroughs due to vaccine inefficiencies and resistance to therapeutic monoclonal antibodies.

"It remains urgent to identify novel therapeutics," Liu said. "We
think evACE2 can meet the challenges and fight against broad strains
of SARS-CoV-2 and future emerging coronaviruses to protect the immunocompromised (at least 2.7% of U.S. adults), unvaccinated (94% in low-income countries and more than 30% in the U.S.) and even vaccinated
from 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 prevention
and treatment of COVID-19. Liu and another co-senior author, Deyu Fang
from pathology at Northwestern, have formed a startup company, Exomira,
to take this patent and develop evACE2 as a therapeutic.

A team of more than 30 authors collaborated on this work. They include
four lead co-first authors Lamiaa El-Shennawy, Andrew Hoffmann and
Nurmaa Dashzeveg, all from the Liu lab at Northwestern, and Kathleen
McAndrews from Raghu Kalluri Lab of MD Anderson. Multiple 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), Drs. 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 M.D. Anderson was fostered
by co- author Valerie LeBleu, an MD/MBA student at Feinberg and Kellogg
School of Management and formerly an 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 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.

========================================================================== Story Source: Materials provided by Northwestern_University. Original
written by Marla Paul.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Lamiaa El-Shennawy, Andrew D. Hoffmann, Nurmaa Khund Dashzeveg,
Kathleen
M. McAndrews, Paul J. Mehl, Daphne Cornish, Zihao Yu, Valerie
L. Tokars, Vlad Nicolaescu, Anastasia Tomatsidou, Chengsheng Mao,
Christopher J.

Felicelli, Chia-Feng Tsai, Carolina Ostiguin, Yuzhi Jia, Lin Li,
Kevin Furlong, Jan Wysocki, Xin Luo, Carolina F. Ruivo, Daniel
Batlle, Thomas J. Hope, Yang Shen, Young Kwang Chae, Hui Zhang,
Valerie S. LeBleu, Tujin Shi, Suchitra Swaminathan, Yuan Luo,
Dominique Missiakas, Glenn C.

Randall, Alexis R. Demonbreun, Michael G. Ison, Raghu Kalluri,
Deyu Fang, Huiping Liu. Circulating ACE2-expressing extracellular
vesicles block broad strains of SARS-CoV-2. Nature Communications,
2022; 13 (1) DOI: 10.1038/s41467-021-27893-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220120091149.htm

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