ADAM10 and ADAM17 promote SARS‐CoV‐2 cell entry and spike protein‐mediated lung cell fusion
| Autor: | Georg Jocher, Vincent Grass, Sarah K Tschirner, Lydia Riepler, Stephan Breimann, Tuğberk Kaya, Madlen Oelsner, M Sabri Hamad, Laura I Hofmann, Carl P Blobel, Carsten B Schmidt‐Weber, Ozgun Gokce, Constanze A Jakwerth, Jakob Trimpert, Janine Kimpel, Andreas Pichlmair, Stefan F Lichtenthaler |
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| Rok vydání: | 2022 |
| Předmět: |
EMBO23
EMBO24 EMBO31 Article Articles A549 apratastat DPC-333 ectodomain shedding syncytia formation genetics [Amyloid Precursor Protein Secretases] ADAM17 Protein 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten genetics [Spike Glycoprotein Coronavirus] Biochemistry Cell Fusion DPC‐333 ADAM10 Protein genetics [ADAM10 Protein] ddc:570 Genetics Humans Lung Molecular Biology SARS-CoV-2 Apratastat Dpc-333 Ectodomain Shedding Syncytia Formation Membrane Proteins COVID-19 Virus Internalization ddc genetics [Membrane Proteins] metabolism [Spike Glycoprotein Coronavirus] Spike Glycoprotein Coronavirus Metalloproteases Angiotensin-Converting Enzyme 2 Amyloid Precursor Protein Secretases metabolism [Membrane Proteins] |
| Zdroj: | EMBO Rep. 23:e54305 (2022) EMBO reports 23(6), e54305 (2022). doi:10.15252/embr.202154305 |
| ISSN: | 1469-3178 1469-221X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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