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

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dc.citation.articleNumber405
dc.citation.journalTitleNature Communications
dc.citation.volumeNumber13
dc.contributor.authorEl-Shennawy, Lamiaa
dc.contributor.authorHoffmann, Andrew D.
dc.contributor.authorDashzeveg, Nurmaa Khund
dc.contributor.authorMcAndrews, Kathleen M.
dc.contributor.authorMehl, Paul J.
dc.contributor.authorCornish, Daphne
dc.contributor.authorYu, Zihao
dc.contributor.authorTokars, Valerie L.
dc.contributor.authorNicolaescu, Vlad
dc.contributor.authorTomatsidou, Anastasia
dc.contributor.authorMao, Chengsheng
dc.contributor.authorFelicelli, Christopher J.
dc.contributor.authorTsai, Chia-Feng
dc.contributor.authorOstiguin, Carolina
dc.contributor.authorJia, Yuzhi
dc.contributor.authorLi, Lin
dc.contributor.authorFurlong, Kevin
dc.contributor.authorWysocki, Jan
dc.contributor.authorLuo, Xin
dc.contributor.authorRuivo, Carolina F.
dc.contributor.authorBatlle, Daniel
dc.contributor.authorHope, Thomas J.
dc.contributor.authorShen, Yang
dc.contributor.authorChae, Young Kwang
dc.contributor.authorZhang, Hui
dc.contributor.authorLeBleu, Valerie S.
dc.contributor.authorShi, Tujin
dc.contributor.authorSwaminathan, Suchitra
dc.contributor.authorLuo, Yuan
dc.contributor.authorMissiakas, Dominique
dc.contributor.authorRandall, Glenn C.
dc.contributor.authorDemonbreun, Alexis R.
dc.contributor.authorIson, Michael G.
dc.contributor.authorKalluri, Raghu
dc.contributor.authorFang, Deyu
dc.contributor.authorLiu, Huiping
dc.date.accessioned2022-02-04T19:19:13Z
dc.date.available2022-02-04T19:19:13Z
dc.date.issued2022
dc.description.abstractThe 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.
dc.identifier.citationEl-Shennawy, Lamiaa, Hoffmann, Andrew D., Dashzeveg, Nurmaa Khund, et al.. "Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2." <i>Nature Communications,</i> 13, (2022) Springer Nature: https://doi.org/10.1038/s41467-021-27893-2.
dc.identifier.digitals41467-021-27893-2
dc.identifier.doihttps://doi.org/10.1038/s41467-021-27893-2
dc.identifier.urihttps://hdl.handle.net/1911/111974
dc.language.isoeng
dc.publisherSpringer Nature
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCirculating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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