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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)
Publ. Version/Full Text Research data 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords A549 ; Apratastat ; Dpc-333 ; Ectodomain Shedding ; Syncytia Formation
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: 23, Issue: 6, Pages: , Article Number: e54305 Supplement: ,
Publisher EMBO Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Allergy Research (IAF)
Grants 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)