Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities

Kruse, T.; Benz, C.; Garvanska, D.H.; Lindqvist, R.; Mihalic, F.; Coscia, F.; Inturi, R.; Sayadi, A.; Simonetti, L.; Nilsson, E.; Ali, M.; Kliche, J.; Moliner Morro, A.; Mund, A.; Andersson, E.; McInerney, G.; Mann, M.; Jemth, P.; Davey, N.E.; Överby, A.K.; Nilsson, J.; Ivarsson, Y.

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities

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Item Type:	Article
Title:	Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Creators Name:	Kruse, T., Benz, C., Garvanska, D.H., Lindqvist, R., Mihalic, F., Coscia, F., Inturi, R., Sayadi, A., Simonetti, L., Nilsson, E., Ali, M., Kliche, J., Moliner Morro, A., Mund, A., Andersson, E., McInerney, G., Mann, M., Jemth, P., Davey, N.E., Överby, A.K., Nilsson, J. and Ivarsson, Y.
Abstract:	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.
Keywords:	Signal Transducing Adaptor Proteins, DNA Helicases, Integration Host Factors, Poly-ADP-Ribose Binding Proteins, RNA Helicases, RNA Recognition Motif Proteins, RNA-Binding Proteins, SARS-CoV-2, Virus Replication / Physiology
Source:	Nature Communications
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	12
Number:	1
Page Range:	6761
Date:	19 November 2021
Official Publication:	https://doi.org/10.1038/s41467-021-26498-z
PubMed:	View item in PubMed

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