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)

tooluniverse-infectious-disease