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Kim, D.-K. ; Weller, B. ; Lin, C.-W. ; Sheykhkarimli, D.* ; Knapp, J.J.* ; Dugied, G.* ; Zanzoni, A.* ; Pons, C.* ; Tofaute, M.J. ; Maseko, S.B.* ; Spirohn, K.* ; Laval, F.* ; Lambourne, L.* ; Kishore, N.* ; Rayhan, A.* ; Sauer, M. ; Young, V. ; Halder, H. ; Marin De La Rosa, N.A. ; Pogoutse, O.* ; Strobel, A. ; Schwehn, P. ; Li, R.* ; Rothballer, S.T. ; Altmann, M. ; Cassonnet, P.* ; Coté, A.G.* ; Elorduy Vergara, L. ; Hazelwood, I.* ; Liu, B.B.* ; Nguyen, M.* ; Pandiarajan, R. ; Dohai, B.S.M. ; Rodriguez, P.A. ; Poirson, J.* ; Giuliana, P.* ; Willems, L.* ; Taipale, M.* ; Jacob, Y.* ; Hao, T.* ; Hill, D.E.* ; Brun, C.* ; Twizere, J.C.* ; Krappmann, D. ; Heinig, M. ; Falter, C. ; Aloy, P.* ; Demeret, C.* ; Vidal, M.* ; Calderwood, M.A.* ; Roth, F.B.* ; Falter-Braun, P.

A proteome-scale map of the SARS-CoV-2-human contactome.

Nat. Biotechnol. 41, 140–149 (2023)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Understanding the mechanisms of coronavirus disease 2019 (COVID-19) disease severity to efficiently design therapies for emerging virus variants remains an urgent challenge of the ongoing pandemic. Infection and immune reactions are mediated by direct contacts between viral molecules and the host proteome, and the vast majority of these virus-host contacts (the 'contactome') have not been identified. Here, we present a systematic contactome map of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the human host encompassing more than 200 binary virus-host and intraviral protein-protein interactions. We find that host proteins genetically associated with comorbidities of severe illness and long COVID are enriched in SARS-CoV-2 targeted network communities. Evaluating contactome-derived hypotheses, we demonstrate that viral NSP14 activates nuclear factor κB (NF-κB)-dependent transcription, even in the presence of cytokine signaling. Moreover, for several tested host proteins, genetic knock-down substantially reduces viral replication. Additionally, we show for USP25 that this effect is phenocopied by the small-molecule inhibitor AZ1. Our results connect viral proteins to human genetic architecture for COVID-19 severity and offer potential therapeutic targets.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2023
Prepublished in Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 1087-0156
e-ISSN 1546-1696
Journal Nature Biotechnology
Quellenangaben Volume: 41, Issue: , Pages: 140–149 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Network Biology (INET)
Institute of Computational Biology (ICB)
Research Unit Signaling and Translation (SAT)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30205 - Bioengineering and Digital Health
Research field(s) Environmental Sciences
Enabling and Novel Technologies
PSP Element(s) G-506400-001
G-553500-001
G-509800-002
G-509000-016
Grants Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH
Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)
DOI 10.1038/s41587-022-01475-z
WOS ID WOS:000865706400003
Scopus ID 85140107745
PubMed ID 36217029
Erfassungsdatum 2022-10-18
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