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