Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly

Nat Commun. 2024 Jan 20;15(1):640. doi: 10.1038/s41467-024-44958-0.


Considerable progress has been made in understanding the molecular host-virus battlefield during SARS-CoV-2 infection. Nevertheless, the assembly and egress of newly formed virions are less understood. To identify host proteins involved in viral morphogenesis, we characterize the proteome of SARS-CoV-2 virions produced from A549-ACE2 and Calu-3 cells, isolated via ultracentrifugation on sucrose cushion or by ACE-2 affinity capture. Bioinformatic analysis unveils 92 SARS-CoV-2 virion-associated host factors, providing a valuable resource to better understand the molecular environment of virion production. We reveal that G3BP1 and G3BP2 (G3BP1/2), two major stress granule nucleators, are embedded within virions and unexpectedly favor virion production. Furthermore, we show that G3BP1/2 participate in the formation of cytoplasmic membrane vesicles, that are likely virion assembly sites, consistent with a proviral role of G3BP1/2 in SARS-CoV-2 dissemination. Altogether, these findings provide new insights into host factors required for SARS-CoV-2 assembly with potential implications for future therapeutic targeting.

MeSH terms

  • COVID-19* / metabolism
  • DNA Helicases / metabolism
  • Humans
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Proteomics
  • RNA Helicases / metabolism
  • RNA Recognition Motif Proteins / metabolism
  • SARS-CoV-2* / metabolism
  • Virion / metabolism
  • Virus Assembly
  • Virus Replication


  • DNA Helicases
  • RNA Recognition Motif Proteins
  • RNA Helicases
  • Poly-ADP-Ribose Binding Proteins
  • G3BP1 protein, human