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.