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

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  • Caroline Benz
  • Richard Lindqvist
  • Filip Mihalic
  • Fabian Coscia
  • Raviteja Inturi
  • Ahmed Sayadi
  • Leandro Simonetti
  • Emma Nilsson
  • Muhammad Ali
  • Johanna Kliche
  • Ainhoa Moliner Morro
  • Eva Andersson
  • Gerald McInerney
  • Per Jemth
  • Norman E Davey
  • Anna K Överby
  • Ylva Ivarsson

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.

Original languageEnglish
Article number6761
JournalNature Communications
Issue number1
Number of pages13
Publication statusPublished - 2021

Bibliographical note

© 2021. The Author(s).

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