A Temporal Interactome Atlas across RNA Viruses reveals Convergent Vulnerabilities for Antiviral Repurposing
- 1Princeton University
Abstract
Viruses remodel host protein interactions to facilitate their replication, yet these dynamic interactomes remain largely unmapped and difficult to compare across infections. Here, to facilitate comparative virology studies, we build the Interactome and Viral Infection Dynamics (InterVir) Atlas, performing thermal proximity coaggregation to profile temporal interactome remodeling across five major RNA viral pathogens. We develop PROTEA, an AI framework that quantifies interactome homology and identifies convergent regulatory hubs. Infection-specific signatures include neuronal SHC1 rewiring associated with altered measles virus replication and dengue-specific secretase interactomes linked to cell-junction remodeling. Comparative virology analyses uncover unexpected interactome convergence between measles and flaviviruses, unobserved in protein-abundance profiling. Mapping these shared regulatory programs to drug targets allowed prioritization of compound repurposing as antivirals. Experimental testing of ten compounds demonstrated antiviral efficacy across multiple infections. Together, InterVir and PROTEA establish an open-access resource for comparative virology, facilitating the identification of conserved host vulnerabilities and drug repurposing.
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BibTeX
@misc{reed2026temporal,
title = {{A Temporal Interactome Atlas across RNA Viruses reveals Convergent Vulnerabilities for Antiviral Repurposing}},
author = {T. J. Reed and A. Tadych and O. G. Troyanskaya and I. M. Cristea},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753288},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753288v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Temporal Interactome Atlas across RNA Viruses reveals Convergent Vulnerabilities for Antiviral Repurposing
AU - T. J. Reed
AU - A. Tadych
AU - O. G. Troyanskaya
AU - I. M. Cristea
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753288
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753288v1
AB - Viruses remodel host protein interactions to facilitate their replication, yet these dynamic interactomes remain largely unmapped and difficult to compare across infections. Here, to facilitate comparative virology studies, we build the Interactome and Viral Infection Dynamics (InterVir) Atlas, performing thermal proximity coaggregation to profile temporal interactome remodeling across five major RNA viral pathogens. We develop PROTEA, an AI framework that quantifies interactome homology and identifies convergent regulatory hubs. Infection-specific signatures include neuronal SHC1 rewiring associated with altered measles virus replication and dengue-specific secretase interactomes linked to cell-junction remodeling. Comparative virology analyses uncover unexpected interactome convergence between measles and flaviviruses, unobserved in protein-abundance profiling. Mapping these shared regulatory programs to drug targets allowed prioritization of compound repurposing as antivirals. Experimental testing of ten compounds demonstrated antiviral efficacy across multiple infections. Together, InterVir and PROTEA establish an open-access resource for comparative virology, facilitating the identification of conserved host vulnerabilities and drug repurposing.
ER -