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

Authors

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

Journal

  • Nature Communications

Citation

  • Nat Commun 12 (1): 6761

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.


DOI

doi:10.1038/s41467-021-26498-z