Infectious Disease Outbreak Intelligence Rapid response system for emerging pathogens using taxonomy analysis, target identification, structure prediction, and computational drug repurposing. KEY PRINCIPLES : Speed is critical - Optimize for rapid actionable intelligence Target essential proteins - Focus on conserved, essential viral/bacterial proteins Leverage existing drugs - Prioritize FDA-approved compounds for repurposing Structure-guided - Use NvidiaNIM for rapid structure prediction and docking Evidence-graded - Grade repurposing candidates by evidence strength Actionable output - Prioritized drug candidates with rationale English-first queries - Always use English terms in tool calls; respond in user's language When to Use Apply when user asks: "New pathogen detected - what drugs might work?" "Emerging virus [X] - therapeutic options?" "Drug repurposing candidates for [pathogen]" "What do we know about [novel coronavirus/bacteria]?" "Essential targets in [pathogen] for drug development" "Can we repurpose [drug] against [pathogen]?" Critical Workflow Requirements 1. Report-First Approach (MANDATORY) Create [PATHOGEN]_outbreak_intelligence.md FIRST with section headers Progressively update as data is gathered Output separate files: [PATHOGEN]_drug_candidates.csv , [PATHOGEN]_target_proteins.csv 2. Citation Requirements (MANDATORY) Every finding must have inline source attribution:
Target: RNA-dependent RNA polymerase (RdRp)
- **
- UniProt
- **
-
P0DTD1 (NSP12)
- **
- Essentiality
- **
- Required for replication
*
Source: UniProt via
UniProt_search, literature review * Phase 0: Tool Verification Known Parameter Corrections Tool WRONG Parameter CORRECT Parameter NCBI_Taxonomy_search name query UniProt_search name query ChEMBL_search_targets target query NvidiaNIM_diffdock protein_file protein (content) Workflow Overview Phase 1: Pathogen Identification ├── Taxonomic classification (NCBI Taxonomy) ├── Closest relatives (for knowledge transfer) ├── Genome/proteome availability └── OUTPUT: Pathogen profile | Phase 2: Target Identification ├── Essential genes/proteins (UniProt) ├── Conservation across strains ├── Druggability assessment (ChEMBL) └── OUTPUT: Prioritized target list (scored by essentiality/conservation/druggability/precedent) | Phase 3: Structure Prediction (NvidiaNIM) ├── AlphaFold2/ESMFold for targets ├── Binding site identification ├── Quality assessment (pLDDT) └── OUTPUT: Target structures (docking-ready if pLDDT > 70) | Phase 4: Drug Repurposing Screen ├── Approved drugs for related pathogens (ChEMBL) ├── Broad-spectrum antivirals/antibiotics ├── Docking screen (NvidiaNIM_diffdock) └── OUTPUT: Ranked candidate drugs | Phase 4.5: Pathway Analysis ├── KEGG: Pathogen metabolism pathways ├── Essential metabolic targets ├── Host-pathogen interaction pathways └── OUTPUT: Pathway-based drug targets | Phase 5: Literature Intelligence ├── PubMed: Published outbreak reports ├── BioRxiv/MedRxiv: Recent preprints (CRITICAL for outbreaks) ├── ArXiv: Computational/ML preprints ├── OpenAlex: Citation tracking ├── ClinicalTrials.gov: Active trials └── OUTPUT: Evidence synthesis | Phase 6: Report Synthesis ├── Top drug candidates with evidence grades ├── Clinical trial opportunities ├── Recommended immediate actions └── OUTPUT: Final report Phase Summaries Phase 1: Pathogen Identification Classify via NCBI Taxonomy (query param). Identify related pathogens with existing drugs for knowledge transfer. Determine genome/proteome availability. Phase 2: Target Identification Search UniProt for pathogen proteins (reviewed). Check ChEMBL for drug precedent. Score targets by: Essentiality (30%), Conservation (25%), Druggability (25%), Drug precedent (20%). Aim for 5+ targets. Phase 3: Structure Prediction Use NvidiaNIM AlphaFold2 for top 3 targets. Assess pLDDT confidence. Only dock structures with pLDDT > 70 (active site > 90 preferred). Fallback: alphafold_get_prediction or NvidiaNIM_esmfold. Phase 4: Drug Repurposing Screen Source candidates from: related pathogen drugs, broad-spectrum antivirals, target class drugs (DGIdb). Dock top 20+ candidates via NvidiaNIM_diffdock. Rank by docking score and evidence tier. Phase 4.5: Pathway Analysis Use KEGG to identify essential metabolic pathways. Map host-pathogen interaction points. Identify pathway-based drug targets beyond direct protein inhibition. Phase 5: Literature Intelligence Search PubMed (peer-reviewed), BioRxiv/MedRxiv (preprints - critical for outbreaks), ArXiv (computational), ClinicalTrials.gov (active trials). Track citations via OpenAlex. Note: preprints are NOT peer-reviewed. Phase 6: Report Synthesis Aggregate all findings into final report. Grade every candidate. Provide 3+ immediate actions, clinical trial opportunities, and research priorities. Evidence Grading Tier Symbol Criteria Example T1 [T1] FDA approved for this pathogen Remdesivir for COVID T2 [T2] Clinical trial evidence OR approved for related pathogen Favipiravir T3 [T3] In vitro activity OR strong docking + mechanism Sofosbuvir T4 [T4] Computational prediction only Novel docking hits Completeness Checklist Phase 1: Pathogen ID Taxonomic classification complete Related pathogens identified Genome/proteome availability noted Phase 2: Targets 5+ targets identified Essentiality documented Conservation assessed Drug precedent checked Phase 3: Structures Structures predicted for top 3 targets pLDDT confidence reported Binding sites identified Phase 4: Drug Screen 20+ candidates screened FDA-approved drugs prioritized Docking scores reported Top 5 candidates detailed Phase 5: Literature Recent papers summarized Active trials listed Resistance data noted Phase 6: Recommendations 3+ immediate actions Clinical trial opportunities Research priorities Fallback Chains Primary Tool Fallback 1 Fallback 2 NvidiaNIM_alphafold2 alphafold_get_prediction NvidiaNIM_esmfold NvidiaNIM_diffdock NvidiaNIM_boltz2 Manual docking NCBI_Taxonomy_search UniProt_taxonomy Manual classification ChEMBL_search_drugs DrugBank_search PubChem bioassays References File Contents TOOLS_REFERENCE.md Complete tool documentation phase_details.md Detailed code examples and procedures for each phase report_template.md Report template with section headers, checklist, and evidence grading CHECKLIST.md Pre-delivery verification checklist (quality, citations, docking) EXAMPLES.md Full worked examples (coronavirus, CRKP, limited-info scenarios)