tooluniverse-infectious-disease

Infectious Disease Outbreak Intelligence

Rapid response system for emerging pathogens using taxonomy analysis, target identification, structure prediction, and computational drug repurposing.

KEY PRINCIPLES:

1. Speed is critical - Optimize for rapid actionable intelligence
2. Target essential proteins - Focus on conserved, essential viral/bacterial proteins
3. Leverage existing drugs - Prioritize FDA-approved compounds for repurposing
4. Structure-guided - Use NvidiaNIM for rapid structure prediction and docking
5. Evidence-graded - Grade repurposing candidates by evidence strength
6. Actionable output - Prioritized drug candidates with rationale
7. English-first queries - Always use English terms in tool calls; respond in user's language

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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]?"

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Critical Workflow Requirements

1. Report-First Approach (MANDATORY)

1. Create [PATHOGEN]_outbreak_intelligence.md FIRST with section headers
2. Progressively update as data is gathered
3. 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*

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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)

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Workflow Overview

Phase 1: Pathogen Identification
├── Taxonomic classification (NCBI Taxonomy)
├── Closest relatives (for knowledge transfer)
├── Genome/proteome availability
└── OUTPUT: Pathogen profile
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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
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Phase 4.5: Pathway Analysis
├── KEGG: Pathogen metabolism pathways
├── Essential metabolic targets
├── Host-pathogen interaction pathways
└── OUTPUT: Pathway-based drug targets
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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

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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.

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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

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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

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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

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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)