Publikationsdatenbank

ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion (2022)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Jocher, Georg

Grass, Vincent

Tschirner, Sarah K.

Riepler, Lydia

Breimann, Stephan

Kaya, Tuğberk

Oelsner, Madlen

Hamad, Sabri

Hofmann, Laura I.

Blobel, Carl P.

Schmidt-Weber, Carsten B.

Gokce, Ozgun

Jakwerth, Constanze A.

Trimpert, Jakob (WE 5)

Kimpel, Janine

Pichlmair, Andreas

Lichtenthaler, Stefan F.

Quelle

EMBO reports

Bandzählung: 23

Heftzählung: 6

Seiten: Artikelnummer: e54305

ISSN: 1469-3178

Sprache

Englisch

Verweise

URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/35527514/

DOI: 10.15252/embr.202154305

Pubmed: 35527514

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.