tetano
Editor, Senior Moderator
Commun Biol
. 2025 Mar 26;8(1):501.
doi: 10.1038/s42003-025-07933-z. Multimodal SARS-CoV-2 interactome sketches the virus-host spatial organization
Guillaume Dugied[SUP] #[/SUP][SUP] 1 2 [/SUP], Estelle Mn Laurent[SUP] #[/SUP][SUP] 3 [/SUP], Mikaël Attia[SUP] #[/SUP][SUP] 1 2 [/SUP], Jean-Pascal Gimeno[SUP] 3 [/SUP], Kamel Bachiri[SUP] 3 [/SUP], Payman Samavarchi-Tehrani[SUP] 4 [/SUP], Flora Donati[SUP] 5 [/SUP], Yannis Rahou[SUP] 1 5 [/SUP], Sandie Munier[SUP] 1 [/SUP], Faustine Amara[SUP] 1 [/SUP], Mélanie Dos Santos[SUP] 1 [/SUP], Nicolas Soler[SUP] 6 [/SUP], Stevenn Volant[SUP] 7 [/SUP], Natalia Pietrosemoli[SUP] 7 [/SUP], Anne-Claude Gingras[SUP] 4 [/SUP], Georgios A Pavlopoulos[SUP] 8 [/SUP], Sylvie van der Werf[SUP] 1 5 [/SUP], Pascal Falter-Braun[SUP] 9 10 [/SUP], Patrick Aloy[SUP] 6 11 [/SUP], Yves Jacob[SUP] 1 [/SUP], Anastassia Komarova[SUP] 1 2 [/SUP], Yorgos Sofianatos[SUP] 12 [/SUP], Etienne Coyaud[SUP] 13 [/SUP], Caroline Demeret[SUP] 14 15 [/SUP]
Affiliations
An accurate spatial representation of protein-protein interaction networks is needed to achieve a realistic and biologically relevant representation of interactomes. Here, we leveraged the spatial information included in Proximity-Dependent Biotin Identification (BioID) interactomes of SARS-CoV-2 proteins to calculate weighted distances and model the organization of the SARS-CoV-2-human interactome in three dimensions (3D) within a cell-like volume. Cell regions with viral occupancy were highlighted, along with the coordination of viral proteins exploiting the cellular machinery. Profiling physical intra-virus and virus-host contacts enabled us to demonstrate both the accuracy and the predictive value of our 3D map for direct interactions, meaning that proteins in closer proximity tend to interact physically. Several functionally important virus-host complexes were detected, and robust structural models were obtained, opening the way to structure-directed drug discovery screens. This PPI discovery pipeline approach brings us closer to a realistic spatial representation of interactomes, which, when applied to viruses or other pathogens, can provide significant information for infection. Thus, it represents a promising tool for coping with emerging infectious diseases.
. 2025 Mar 26;8(1):501.
doi: 10.1038/s42003-025-07933-z. Multimodal SARS-CoV-2 interactome sketches the virus-host spatial organization
Guillaume Dugied[SUP] #[/SUP][SUP] 1 2 [/SUP], Estelle Mn Laurent[SUP] #[/SUP][SUP] 3 [/SUP], Mikaël Attia[SUP] #[/SUP][SUP] 1 2 [/SUP], Jean-Pascal Gimeno[SUP] 3 [/SUP], Kamel Bachiri[SUP] 3 [/SUP], Payman Samavarchi-Tehrani[SUP] 4 [/SUP], Flora Donati[SUP] 5 [/SUP], Yannis Rahou[SUP] 1 5 [/SUP], Sandie Munier[SUP] 1 [/SUP], Faustine Amara[SUP] 1 [/SUP], Mélanie Dos Santos[SUP] 1 [/SUP], Nicolas Soler[SUP] 6 [/SUP], Stevenn Volant[SUP] 7 [/SUP], Natalia Pietrosemoli[SUP] 7 [/SUP], Anne-Claude Gingras[SUP] 4 [/SUP], Georgios A Pavlopoulos[SUP] 8 [/SUP], Sylvie van der Werf[SUP] 1 5 [/SUP], Pascal Falter-Braun[SUP] 9 10 [/SUP], Patrick Aloy[SUP] 6 11 [/SUP], Yves Jacob[SUP] 1 [/SUP], Anastassia Komarova[SUP] 1 2 [/SUP], Yorgos Sofianatos[SUP] 12 [/SUP], Etienne Coyaud[SUP] 13 [/SUP], Caroline Demeret[SUP] 14 15 [/SUP]
Affiliations
- PMID: 40140549
- DOI: 10.1038/s42003-025-07933-z
An accurate spatial representation of protein-protein interaction networks is needed to achieve a realistic and biologically relevant representation of interactomes. Here, we leveraged the spatial information included in Proximity-Dependent Biotin Identification (BioID) interactomes of SARS-CoV-2 proteins to calculate weighted distances and model the organization of the SARS-CoV-2-human interactome in three dimensions (3D) within a cell-like volume. Cell regions with viral occupancy were highlighted, along with the coordination of viral proteins exploiting the cellular machinery. Profiling physical intra-virus and virus-host contacts enabled us to demonstrate both the accuracy and the predictive value of our 3D map for direct interactions, meaning that proteins in closer proximity tend to interact physically. Several functionally important virus-host complexes were detected, and robust structural models were obtained, opening the way to structure-directed drug discovery screens. This PPI discovery pipeline approach brings us closer to a realistic spatial representation of interactomes, which, when applied to viruses or other pathogens, can provide significant information for infection. Thus, it represents a promising tool for coping with emerging infectious diseases.