Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities. / Kruse, Thomas; Benz, Caroline; Garvanska, Dimitriya H; Lindqvist, Richard; Mihalic, Filip; Coscia, Fabian; Inturi, Raviteja; Sayadi, Ahmed; Simonetti, Leandro; Nilsson, Emma; Ali, Muhammad; Kliche, Johanna; Moliner Morro, Ainhoa; Mund, Andreas; Andersson, Eva; McInerney, Gerald; Mann, Matthias; Jemth, Per; Davey, Norman E; Överby, Anna K; Nilsson, Jakob; Ivarsson, Ylva.
I: Nature Communications, Bind 12, Nr. 1, 6761, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
AU - Kruse, Thomas
AU - Benz, Caroline
AU - Garvanska, Dimitriya H
AU - Lindqvist, Richard
AU - Mihalic, Filip
AU - Coscia, Fabian
AU - Inturi, Raviteja
AU - Sayadi, Ahmed
AU - Simonetti, Leandro
AU - Nilsson, Emma
AU - Ali, Muhammad
AU - Kliche, Johanna
AU - Moliner Morro, Ainhoa
AU - Mund, Andreas
AU - Andersson, Eva
AU - McInerney, Gerald
AU - Mann, Matthias
AU - Jemth, Per
AU - Davey, Norman E
AU - Överby, Anna K
AU - Nilsson, Jakob
AU - Ivarsson, Ylva
N1 - © 2021. The Author(s).
PY - 2021
Y1 - 2021
N2 - Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
AB - Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
U2 - 10.1038/s41467-021-26498-z
DO - 10.1038/s41467-021-26498-z
M3 - Journal article
C2 - 34799561
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6761
ER -
ID: 285718968