Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2

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 () and Huiping Liu ()
Additional contact information
Lamiaa El-Shennawy: Northwestern University Feinberg School of Medicine
Andrew D. Hoffmann: Northwestern University Feinberg School of Medicine
Nurmaa Khund Dashzeveg: Northwestern University Feinberg School of Medicine
Kathleen M. McAndrews: The University of Texas MD Anderson Cancer Center
Paul J. Mehl: Northwestern University Feinberg School of Medicine
Daphne Cornish: Northwestern University Feinberg School of Medicine
Zihao Yu: Northwestern University Feinberg School of Medicine
Valerie L. Tokars: Northwestern University Feinberg School of Medicine
Vlad Nicolaescu: The University of Chicago Howard T. Ricketts Laboratory and Department of Microbiology
Anastasia Tomatsidou: The University of Chicago Howard T. Ricketts Laboratory and Department of Microbiology
Chengsheng Mao: Northwestern University Feinberg School of Medicine
Christopher J. Felicelli: Northwestern University Feinberg School of Medicine
Chia-Feng Tsai: Pacific Northwest National Laboratory
Carolina Ostiguin: Northwestern University Feinberg School of Medicine
Yuzhi Jia: Northwestern University Feinberg School of Medicine
Lin Li: Northwestern University Feinberg School of Medicine
Kevin Furlong: The University of Chicago Howard T. Ricketts Laboratory and Department of Microbiology
Jan Wysocki: Northwestern University Feinberg School of Medicine
Xin Luo: The University of Texas MD Anderson Cancer Center
Carolina F. Ruivo: The University of Texas MD Anderson Cancer Center
Daniel Batlle: Northwestern University Feinberg School of Medicine
Thomas J. Hope: Northwestern University Feinberg School of Medicine
Yang Shen: Texas A&M University
Young Kwang Chae: Northwestern University Feinberg School of Medicine
Hui Zhang: Northwestern University Feinberg School of Medicine
Valerie S. LeBleu: Northwestern University Feinberg School of Medicine
Tujin Shi: Pacific Northwest National Laboratory
Suchitra Swaminathan: Northwestern University Feinberg School of Medicine
Yuan Luo: Northwestern University Feinberg School of Medicine
Dominique Missiakas: The University of Chicago Howard T. Ricketts Laboratory and Department of Microbiology
Glenn C. Randall: The University of Chicago Howard T. Ricketts Laboratory and Department of Microbiology
Alexis R. Demonbreun: Northwestern University Feinberg School of Medicine
Michael G. Ison: Northwestern University Feinberg School of Medicine
Raghu Kalluri: The University of Texas MD Anderson Cancer Center
Deyu Fang: Northwestern University Feinberg School of Medicine
Huiping Liu: Northwestern University Feinberg School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of the coronavirus induced disease 2019 (COVID-19) with evolving variants of concern. It remains urgent to identify novel approaches against broad strains of SARS-CoV-2, which infect host cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). Herein, we report an increase in circulating extracellular vesicles (EVs) that express ACE2 (evACE2) in plasma of COVID-19 patients, which levels are associated with severe pathogenesis. Importantly, evACE2 isolated from human plasma or cells neutralizes SARS-CoV-2 infection by competing with cellular ACE2. Compared to vesicle-free recombinant human ACE2 (rhACE2), evACE2 shows a 135-fold higher potency in blocking the binding of the viral spike protein RBD, and a 60- to 80-fold higher efficacy in preventing infections by both pseudotyped and authentic SARS-CoV-2. Consistently, evACE2 protects the hACE2 transgenic mice from SARS-CoV-2-induced lung injury and mortality. Furthermore, evACE2 inhibits the infection of SARS-CoV-2 variants (α, β, and δ) with equal or higher potency than for the wildtype strain, supporting a broad-spectrum antiviral mechanism of evACE2 for therapeutic development to block the infection of existing and future coronaviruses that use the ACE2 receptor.

Date: 2022
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Citations: View citations in EconPapers (2)

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DOI: 10.1038/s41467-021-27893-2

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