tetano
Editor, Senior Moderator
Nat Commun
. 2021 Nov 19;12(1):6761.
doi: 10.1038/s41467-021-26498-z.
Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Thomas Kruse[SUP] #[/SUP][SUP] 1 [/SUP], Caroline Benz[SUP] #[/SUP][SUP] 2 [/SUP], Dimitriya H Garvanska[SUP] #[/SUP][SUP] 1 [/SUP], Richard Lindqvist[SUP] #[/SUP][SUP] 3 4 [/SUP], Filip Mihalic[SUP] 5 [/SUP], Fabian Coscia[SUP] 1 6 [/SUP], Raviteja Inturi[SUP] 5 [/SUP], Ahmed Sayadi[SUP] 2 [/SUP], Leandro Simonetti[SUP] 2 [/SUP], Emma Nilsson[SUP] 3 4 [/SUP], Muhammad Ali[SUP] 2 [/SUP], Johanna Kliche[SUP] 2 [/SUP], Ainhoa Moliner Morro[SUP] 7 [/SUP], Andreas Mund[SUP] 1 [/SUP], Eva Andersson[SUP] 5 [/SUP], Gerald McInerney[SUP] 7 [/SUP], Matthias Mann[SUP] 1 [/SUP], Per Jemth[SUP] 5 [/SUP], Norman E Davey[SUP] 8 [/SUP], Anna K Överby[SUP] 9 10 [/SUP], Jakob Nilsson[SUP] 11 [/SUP], Ylva Ivarsson[SUP] 12 [/SUP]
Affiliations
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.
. 2021 Nov 19;12(1):6761.
doi: 10.1038/s41467-021-26498-z.
Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Thomas Kruse[SUP] #[/SUP][SUP] 1 [/SUP], Caroline Benz[SUP] #[/SUP][SUP] 2 [/SUP], Dimitriya H Garvanska[SUP] #[/SUP][SUP] 1 [/SUP], Richard Lindqvist[SUP] #[/SUP][SUP] 3 4 [/SUP], Filip Mihalic[SUP] 5 [/SUP], Fabian Coscia[SUP] 1 6 [/SUP], Raviteja Inturi[SUP] 5 [/SUP], Ahmed Sayadi[SUP] 2 [/SUP], Leandro Simonetti[SUP] 2 [/SUP], Emma Nilsson[SUP] 3 4 [/SUP], Muhammad Ali[SUP] 2 [/SUP], Johanna Kliche[SUP] 2 [/SUP], Ainhoa Moliner Morro[SUP] 7 [/SUP], Andreas Mund[SUP] 1 [/SUP], Eva Andersson[SUP] 5 [/SUP], Gerald McInerney[SUP] 7 [/SUP], Matthias Mann[SUP] 1 [/SUP], Per Jemth[SUP] 5 [/SUP], Norman E Davey[SUP] 8 [/SUP], Anna K Överby[SUP] 9 10 [/SUP], Jakob Nilsson[SUP] 11 [/SUP], Ylva Ivarsson[SUP] 12 [/SUP]
Affiliations
- PMID: 34799561
- DOI: 10.1038/s41467-021-26498-z
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.