From drug repurposing to antiviral activity expansion: building antiviral maps from multiple viral trees

We propose an evidence-weighted atlas for drug repurposing and antiviral activity expansion. Instead of using a universal viral phylogeny, our framework matches the way in which viruses are represented to the pharmacological question being asked. The atlas integrates five distinct layers: closely related viruses are represented in whole-genome trees, homologous drug targets in target-specific polymerase or protease trees, deeply diverged virion proteins in structure-derived trees, convergent cellular vulnerabilities in host-dependency networks, and a complementary view of chemical space, linking scaffold variation to breadth, potency and resistance liability, in antiviral structure-activity relationship trees. Candidate drug or activity transfers are filtered by pocket conservation, intracellular activation, tissue exposure, safety and resistance barriers. Successful and failed combinations calibrate the framework, which prioritizes the smallest justified 2-4-agent regimen for untreated viruses and Pathogen X.