Integrated Biosciences unveiled an optogenetics-based screening platform allowing precise temporal and spatial modulation of cell signaling pathways. Applying it to the integrated stress response (ISR), the platform screened over 370,000 compounds to identify selective ISR modulators that enhance apoptosis sensitization without cytotoxicity. A lead compound targeting GCN2 showed broad-spectrum antiviral activity in vivo. This innovative technology offers a powerful tool for discovering high-precision therapeutics with previously inaccessible mechanisms of action.