Proteome-based network medicine identifies Gabapentin as a drug to restore viro-induced perturbations of brain circuitryProteome-based network medicine identifies Gabapentin as a drug to restore viro-induced perturbations of brain circuitry

ABSTRACT: The development of antivirals mostly focuses on viro-centric approaches, but the need for small molecules capable of alleviating the functional perturbations of a tissue induced upon infection is lagging behind. This symptom-oriented complementary strategy used to suffer from the lack of appropriate approaches to study it, but the development of more physiological 3D models coupled to the advent of omic-based network medicine approaches offers new opportunities for drug discovery. Here, we characterized the proteomic-based perturbome of human cerebral organoids (hCO) infected by the bunyavirus Tahyna (TAHV), and highlighted the major impact of the infection on neural pathways and down-modulation of synapse-associated proteins. Furthermore, proteome network analysis identified Gabapentin (GBP) as a treatment that prevents the TAHV-induced perturbation of electrical activity in hCO and ex vivo human brain explants, while GBP does not inhibit virus replication itself. This seminal work provides an original pipeline for symptom-oriented antiviral drug discovery.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Orthobunyavirus

TISSUE(S): Brain, Embryonic Stem Cell

SUBMITTER: Francois Delalande  

LAB HEAD: Christine Carapito

PROVIDER: PXD058349 | Pride | 2026-07-24

REPOSITORIES: Pride