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

El-Shennawy, Lamiaa; Hoffmann, Andrew D.; Dashzeveg, Nurmaa Khund; McAndrews, Kathleen M.; Mehl, Paul J.; Cornish, Daphne; Yu, Zihao; Tokars, Valerie L.; Nicolaescu, Vlad; Tomatsidou, Anastasia; Mao, Chengsheng; Felicelli, Christopher J.; Tsai, Chia-Feng; Ostiguin, Carolina; Jia, Yuzhi; Li, Lin; Furlong, Kevin; Wysocki, Jan; Luo, Xin; Ruivo, Carolina F.; Batlle, Daniel; Hope, Thomas J.; Shen, Yang; Chae, Young Kwang; Zhang, Hui; LeBleu, Valerie S.; Shi, Tujin; Swaminathan, Suchitra; Luo, Yuan; Missiakas, Dominique; Randall, Glenn C.; Demonbreun, Alexis R.; Ison, Michael G.; Kalluri, Raghu; Fang, Deyu; Liu, Huiping

doi:10.1038/s41467-021-27893-2

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

Journal Article · Thu Jan 20 00:00:00 EST 2022 · Nature Communications

DOI:https://doi.org/10.1038/s41467-021-27893-2· OSTI ID:1846287

El-Shennawy, Lamiaa ^[1]; Hoffmann, Andrew D. ^[1]; Dashzeveg, Nurmaa Khund ^[1]; ^[2]; Mehl, Paul J. ^[3]; ^[1]; Yu, Zihao ^[1]; Tokars, Valerie L. ^[1]; Nicolaescu, Vlad ^[4]; Tomatsidou, Anastasia ^[4]; ^[3]; Felicelli, Christopher J. ^[3]; Tsai, Chia-Feng ^[3]; Ostiguin, Carolina ^[3]; Jia, Yuzhi ^[1]; Li, Lin ^[3]; Furlong, Kevin ^[4]; Wysocki, Jan ^[3]; Luo, Xin ^[2]; Ruivo, Carolina F. ^[2] more »

Northwestern Univ., Chicago, IL (United States)
Univ. of Texas MD Anderson Cancer Center, Houston, TX (United States)
Northwestern Univ. Feinberg School of Medicine, Chicago, IL (United States)
Univ. of Chicago Howard T. Ricketts Lab. and Department of Microbiology, Chicago, IL (United States)
Texas A & M Univ., College Station, TX (United States)
Northwestern Univ., Chicago, IL (United States); Univ. of Texas MD Anderson Cancer Center, Houston, TX (United States); Northwestern Univ., Evanston, IL (United States)
Univ. of Texas MD Anderson Cancer Center, Houston, TX (United States); Rice Univ., Houston, TX (United States); Baylor College of Medicine, Houston, TX (United States)
Northwestern Univ., Chicago, IL (United States); Northwestern Univ. Feinberg School of Medicine, Chicago, IL (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1846287

Report Number(s):: PNNL-SA-169658

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 13; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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