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

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dc.citation.articleNumber405en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber13en_US
dc.contributor.authorEl-Shennawy, Lamiaaen_US
dc.contributor.authorHoffmann, Andrew D.en_US
dc.contributor.authorDashzeveg, Nurmaa Khunden_US
dc.contributor.authorMcAndrews, Kathleen M.en_US
dc.contributor.authorMehl, Paul J.en_US
dc.contributor.authorCornish, Daphneen_US
dc.contributor.authorYu, Zihaoen_US
dc.contributor.authorTokars, Valerie L.en_US
dc.contributor.authorNicolaescu, Vladen_US
dc.contributor.authorTomatsidou, Anastasiaen_US
dc.contributor.authorMao, Chengshengen_US
dc.contributor.authorFelicelli, Christopher J.en_US
dc.contributor.authorTsai, Chia-Fengen_US
dc.contributor.authorOstiguin, Carolinaen_US
dc.contributor.authorJia, Yuzhien_US
dc.contributor.authorLi, Linen_US
dc.contributor.authorFurlong, Kevinen_US
dc.contributor.authorWysocki, Janen_US
dc.contributor.authorLuo, Xinen_US
dc.contributor.authorRuivo, Carolina F.en_US
dc.contributor.authorBatlle, Danielen_US
dc.contributor.authorHope, Thomas J.en_US
dc.contributor.authorShen, Yangen_US
dc.contributor.authorChae, Young Kwangen_US
dc.contributor.authorZhang, Huien_US
dc.contributor.authorLeBleu, Valerie S.en_US
dc.contributor.authorShi, Tujinen_US
dc.contributor.authorSwaminathan, Suchitraen_US
dc.contributor.authorLuo, Yuanen_US
dc.contributor.authorMissiakas, Dominiqueen_US
dc.contributor.authorRandall, Glenn C.en_US
dc.contributor.authorDemonbreun, Alexis R.en_US
dc.contributor.authorIson, Michael G.en_US
dc.contributor.authorKalluri, Raghuen_US
dc.contributor.authorFang, Deyuen_US
dc.contributor.authorLiu, Huipingen_US
dc.date.accessioned2022-02-04T19:19:13Zen_US
dc.date.available2022-02-04T19:19:13Zen_US
dc.date.issued2022en_US
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.en_US
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.en_US
dc.identifier.digitals41467-021-27893-2en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-021-27893-2en_US
dc.identifier.urihttps://hdl.handle.net/1911/111974en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
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.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleCirculating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2en_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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