Article (Scientific journals)
A proteome-scale map of the SARS-CoV-2–human contactome
Kim, Dae-Kyum; Weller, Benjamin; Lin, Chung-Wen et al.
2022In Nature Biotechnology, 41 (1), p. 140-149
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Keywords :
Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology
Abstract :
[en] 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.
Disciplines :
Immunology & infectious disease
Author, co-author :
Kim, Dae-Kyum
Weller, Benjamin 
Lin, Chung-Wen
Sheykhkarimli, Dayag 
Knapp, Jennifer J. 
Dugied, Guillaume 
Zanzoni, Andreas 
Pons, Carles
Tofaute, Marie J. 
Maseko, Sibusiso Bonginkhost ;  Université de Liège - ULiège > Département GxABT > Microbial technologies
Spirohn, Kerstin 
Laval, Florent  ;  Université de Liège - ULiège > TERRA Research Centre
Lambourne, Luke 
Kishore, Nishka
Rayhan, Ashyad
Sauer, Mayra
Young, Veronika 
Halder, Hridi
la Rosa, Nora Marín-de
Pogoutse, Oxana
Strobel, Alexandra
Schwehn, Patrick
Li, Roujia
Rothballer, Simin T.
Altmann, Melina
Cassonnet, Patricia
Coté, Atina G.
Vergara, Lena Elorduy
Hazelwood, Isaiah
Liu, Betty B.
Nguyen, Maria
Pandiarajan, Ramakrishnan
Dohai, Bushra
Coloma, Patricia A. Rodriguez
Poirson, Juline 
Giuliana, Paolo 
Willems, Luc  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Cellular and Molecular Epigenetics
Taipale, Mikko 
Jacob, Yves 
Hao, Tong 
Hill, David E. 
Brun, Christine 
Twizere, Jean-Claude  ;  Université de Liège - ULiège > GIGA > GIGA Molecular Biology of Diseases - Viral Interactomes Network
Krappmann, Daniel 
Heinig, Matthias
Falter, Claudia
Aloy, Patrick
Demeret, Caroline
Vidal, Marc
Calderwood, Michael A. 
Roth, Frederick P. 
Falter-Braun, Pascal 
More authors (42 more) Less
Language :
Title :
A proteome-scale map of the SARS-CoV-2–human contactome
Publication date :
10 October 2022
Journal title :
Nature Biotechnology
Publisher :
Springer Science and Business Media LLC
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
BAEF - Belgian American Educational Foundation [BE]
Télévie [BE]
Funding number :
Fonds de la Recherche Scientifique (FRS-FNRS) grant PER-40003579
Funding text :
We thank P. Charneau for the hACE2 lentivirus. This work was supported by a Canadian Institutes for Health Research Foundation Grant (F.P.R.), the Canada Excellence Research Chairs Program (F.P.R.), the Thistledown Foundation (F.P.R.); the LabEx Integrative Biology of Emerging Infectious Diseases (10-LABX-0062; Y.J., C.D.) and Platform for European Preparedness Against (Re-)emerging Epidemics, EU (602525; Y.J. and C.D.), the European Union’s Horizon 2020 Research and Innovation Programme (Project ID 101003633, RiPCoN; P.F.-B., C.B., P.A.), HDHL-INTIMIC ‘Interrelation of the Intestinal Microbiome, Diet and Health’ (BMBF Project ID 01EA1803; P.F.-B.), the Free State of Bavaria’s AI for Therapy (AI4T) Initiative through the Institute of AI for Drug Discovery (AID) (P.F.-B.) and Fonds de la Recherche Scientifique (FRS-FNRS) grant PER-40003579 (J.-C.T., L.W.). F.L. was supported by a Belgian American Educational Foundation doctoral research fellowship, a Wallonia-Brussels International (WBI)-World Excellence fellowship and Fonds de la Recherche Scientifique (FRS-FNRS)-Télévie grant FC31747 (Crédit n° 7459421F). M.V. is a Chercheur Qualifié Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium). C.P. was supported by a Ramon y Cajal fellowship (RYC-2017–22959). G.D. was supported by the Ministère de l’Education Nationale, de la Recherche et de l’Innovation with a fellowship from Université Paris Cité.
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