Pathogen-informed therapeutic design: Translating host-control functions into pharmacological strategies

Pathogens deploy specialized mechanisms for tissue entry, barrier crossing, intracellular rerouting, immune remodeling, and persistence within hostile host environments. Although these mechanisms are most often studied in the context of pathogenesis, they also reveal how biological activities can be positioned, routed, sustained, and constrained under the spatial, temporal, immune, metabolic, and tissue-specific pressures encountered in vivo. This Review develops a pathogen-informed design framework for identifying host-facing pathogen functions that can be mechanistically separated from replication, immune evasion, inflammatory amplification, cytotoxic remodeling, or tissue damage and redirected toward therapeutic execution. We examine how computational analysis can expand and prioritize the searchable space of pathogen-derived functions and how experimental profiling can determine whether predicted host engagement, functional output, and controllable activity are supported under relevant biological conditions. We then assess preclinical and clinically implemented examples to determine how far these principles have progressed toward therapeutic use and where translational constraints remain. Current evidence supports individual analytical, engineering, pharmacological, and clinical advances, but these remain distributed across different pathogen systems and therapeutic modalities rather than forming a continuous discovery-to-clinic trajectory. Pathogen-informed therapeutic design therefore provides a function-centered basis for identifying pathogen-derived activities that can be transferred from infection biology into therapeutically controllable settings.