Pathogen-informed therapeutic design: Translating host-control functions into pharmacological strategies - 07/11/26

Abstract |
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Conceptual framework for pathogen-informed therapeutic design. Schematic overview of pathogen-informed therapeutic design. Pathogen functions involved in host-cell entry, membrane crossing, intracellular routing, protein-state modulation, immune-signaling control, and barrier interaction are treated as potential sources of host-control operations rather than directly transferable therapeutic modules. Computational prioritization and experimental profiling are used to assess their host interface, execution context, functional output, and separability from pathogen-associated liabilities. Candidate functions supported across these dimensions can inform therapeutic design variables for modalities constrained by localization, intracellular routing, context-dependent activity, functional output, or safety.
Conceptual framework for pathogen-informed therapeutic design. Schematic overview of pathogen-informed therapeutic design. Pathogen functions involved in host-cell entry, membrane crossing, intracellular routing, protein-state modulation, immune-signaling control, and barrier interaction are treated as potential sources of host-control operations rather than directly transferable therapeutic modules. Computational prioritization and experimental profiling are used to assess their host interface, execution context, functional output, and separability from pathogen-associated liabilities. Candidate functions supported across these dimensions can inform therapeutic design variables for modalities constrained by localization, intracellular routing, context-dependent activity, functional output, or safety. Le texte complet de cet article est disponible en PDF.
Highlights |
• | Pathogen-informed design uncovers host-control functions in pathogen biology. |
• | Host-control functions are discrete pathogen-directed operations on host state. |
• | Computational analysis and experimental profiling prioritize therapeutic candidates. |
• | Pharmacological feasibility depends on exposure, engagement, and safety range. |
• | Preclinical and clinical examples show advances but no end-to-end path. |
Keywords : Pathogen-informed therapeutic design, Host–pathogen interactions, Host-control functions, Artificial intelligence–driven analysis, In vivo therapeutic execution
Plan
Vol 204
Article 119932- novembre 2026 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?
