Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2.
A549 Cells
Angiotensin-Converting Enzyme 2
/ genetics
Animals
COVID-19
/ blood
Chlorocebus aethiops
Extracellular Vesicles
/ genetics
HEK293 Cells
HeLa Cells
Humans
Mice, Transgenic
Neutralization Tests
/ methods
Pandemics
/ prevention & control
Protein Binding
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
/ genetics
Survival Analysis
Vero Cells
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 01 2022
20 01 2022
Historique:
received:
19
09
2021
accepted:
23
12
2021
entrez:
21
1
2022
pubmed:
22
1
2022
medline:
8
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35058437
doi: 10.1038/s41467-021-27893-2
pii: 10.1038/s41467-021-27893-2
pmc: PMC8776790
doi:
Substances chimiques
Spike Glycoprotein, Coronavirus
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
405Subventions
Organisme : NIH HHS
ID : 1S10OD011996-01
Pays : United States
Organisme : NIH HHS
ID : S10 OD011996
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA213233
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NIMH NIH HHS
ID : R03 MH084162
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA257345
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI060915
Pays : United States
Informations de copyright
© 2022. The Author(s).
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