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Jocher, G.* ; Grass, V.* ; Tschirner, S.K.* ; Riepler, L.* ; Breimann, S.* ; Kaya, T.* ; Oelsner, M. ; Hamad, M.S.* ; Hofmann, L.I.* ; Blobel, C.P.* ; Schmidt-Weber, C.B. ; Gokce, O.* ; Jakwerth, C.A. ; Trimpert, J.* ; Kimpel, J.* ; Pichlmair, A.* ; Lichtenthaler, S.F.*

ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion.

EMBO Rep. 23:e54305 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) is the causative agent of COVID-19, but host cell factors contributing to COVID-19 pathogenesis remain only partly understood. We identify the host metalloprotease ADAM17 as a facilitator of SARS-CoV-2 cell entry and the metalloprotease ADAM10 as a host factor required for lung cell syncytia formation, a hallmark of COVID-19 pathology. ADAM10 and ADAM17, which are broadly expressed in the human lung, cleave the SARS-CoV-2 spike protein (S) in vitro, indicating that ADAM10 and ADAM17 contribute to the priming of S, an essential step for viral entry and cell fusion. ADAM protease-targeted inhibitors severely impair lung cell infection by the SARS-CoV-2 variants of concern alpha, beta, delta, and omicron and also reduce SARS-CoV-2 infection of primary human lung cells in a TMPRSS2 protease-independent manner. Our study establishes ADAM10 and ADAM17 as host cell factors for viral entry and syncytia formation and defines both proteases as potential targets for antiviral drug development.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter A549 ; Apratastat ; Dpc-333 ; Ectodomain Shedding ; Syncytia Formation
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Zeitschrift EMBO Reports
Quellenangaben Band: 23, Heft: 6, Seiten: , Artikelnummer: e54305 Supplement: ,
Verlag EMBO Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Förderungen Bayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunst (Bavarian State Ministry of Science and Arts)
Deutsche Forschungsgemeinschaft (DFG)
Bundesministerium fur Bildung und Forschung (BMBF)