Respiratory Infections Curation Project

Overview

This project organizes dismech curation of infections of the respiratory tract — by anatomical site and clinical syndrome rather than by drug class. It is the disease-domain complement to the three drug-mechanism projects:

• ANTIMICROBIAL — antibacterial drug–bug mechanism modules
• ANTIVIRAL — antiviral drug–virus mechanism modules
• ANTIFUNGAL — antifungal mechanism modules

Where those projects ask "how does the drug work against the pathogen," this project asks "what is the pathophysiology of infection at this site, in this host." A respiratory-infection entry should still conforms_to the relevant drug-mechanism module(s) for its treatments; this project tracks the clinical entities and their coverage, and the drug-mechanism projects track the treatment wiring.

Funding alignment: the Intercept initiative

Intercept is a $500M philanthropic fund whose stated goal is to radically reduce and ultimately eliminate endemic respiratory infections — pushing the effective reproduction number below 1 for viruses with R₀ < 3. Its scientific thesis directly shapes the priorities of this project.

Intercept's four core target viruses are all already curated in dismech and seeded above: Influenza, COVID-19 (SARS-CoV-2), Respiratory Syncytial Virus Infection, and Rhinovirus_Infection. So Intercept-aligned work here is primarily about deepening mechanism and treatment coverage, not creating the core entries.

Intercept funds two product classes:

1. Broad-Spectrum Preventatives (BSPs) across five mechanistic tracks: - Adaptive immunity — universal vaccines, broadly-neutralizing antibodies, tissue-resident CD8 T cells (dismech: VACCINE / MONOCLONAL_ANTIBODY modalities) - Direct-acting antivirals — siRNA, broad-spectrum RdRp inhibitors, mAbs, receptor decoys (dismech: existing viral_polymerase_inhibition, viral_entry_fusion_inhibition modules) - Innate-immunity modulators — engineered interferon, cGAS/RIG-I agonists (module gap — see below) - Host-directed antivirals — targeting host dependency factors (module gap — see below) - Physical-barrier formulations — lectin/mucin nasal sprays (a treatment modality)
2. Air Cleaning Technologies (far-UVC, filtration, antimicrobial vapors) — environmental interventions, out of dismech's disease-mechanism scope.

Intercept-aligned mechanism modules

dismech already has seven direct-acting antiviral mechanism modules (polymerase, protease, entry/fusion, integrase, assembly/release, latency, PARP-macrodomain). Two of Intercept's BSP tracks previously had no module; both are now built and validated (schema + terms + independent snippet-substring verification of every evidence quote):

• host_directed_antiviral_dependency ✓ — host dependency factors a virus requires (ACE2 receptor + TMPRSS2 protease for SARS-CoV-2 as the worked example). Target of the host-directed and receptor-decoy tracks; high broad-spectrum value because host factors are conserved where viral proteins are not. Captures the higher resistance barrier, the broad-spectrum consequence, and the host-route-escape / on-target-toxicity limits. Key conformance/treatment target: host_directed_antiviral_dependency#Host Receptor and Protease Engagement.
• innate_antiviral_interferon_response ✓ — viral PAMP sensing (RIG-I/MDA5, cGAS-STING, TLRs) → type I/III interferon induction and JAK-STAT signaling → ISG antiviral state → restriction of replication, with the viral-interferon- antagonism evasion branch (influenza NS1). Target of the innate-immunity-modulator track; the worked therapeutic is peginterferon lambda. Key conformance/treatment target: innate_antiviral_interferon_response#Interferon-Stimulated Gene Antiviral State.

Worked conformers (wired): - host_directed_antiviral_dependency#Host Receptor and Protease Engagement ← COVID-19 (SARS-CoV-2 spike entry via ACE2/TMPRSS2). - innate_antiviral_interferon_response#Viral PAMP Sensing by Pattern-Recognition Receptors ← Influenza (TLR sensing / innate activation). - innate_antiviral_interferon_response#Interferon-Stimulated Gene Antiviral State ← Rhinovirus Infection, Parainfluenza Virus Infection, Human Metapneumovirus Infection, Seasonal Coronavirus Infection, and Adenovirus Respiratory Infection (epithelial innate/interferon antiviral response). - host_directed_antiviral_dependency#Host Receptor and Protease Engagement ← Middle East Respiratory Syndrome (MERS-CoV spike entry via the DPP4 host receptor — the coronavirus parallel to SARS-CoV-2/ACE2). - intracellular_pathogen_persistence (Intracellular Niche + Cell-Penetrant Antimicrobial nodes) ← Legionnaires Disease (macrolide/fluoroquinolone therapy). - bacterial_cell_wall_synthesis_inhibition#Intrinsic Resistance in Cell-Wall-Deficient Organisms and bacterial_protein_synthesis_inhibition (ribosome target + resistance) ← Mycoplasma Pneumoniae Pneumonia (the flagship cell-wall-deficient conformer). - bacterial_protein_synthesis_inhibition (ribosomal macrolide target + resistance) ← Pertussis (toxin-mediated whooping cough; macrolide therapy). - bacterial_cell_wall_synthesis_inhibition (PBP beta-lactam target + acquired resistance) ← Pneumococcal Pneumonia (the typical/cell-walled counterpart to the cell-wall-deficient Mycoplasma). - intracellular_pathogen_persistence + bacterial_protein_synthesis_inhibition (tetracycline target) ← Q Fever (intracellular; doxycycline, mirroring Murine_Typhus). - intracellular_pathogen_persistence + bacterial_protein_synthesis_inhibition (tetracycline target) ← Psittacosis (avian zoonotic intracellular chlamydial pneumonia).

Treatment enrichment (wired): - COVID-19 — Peginterferon Lambda (NCIT:C166435), an interferon-based innate-immunity modulator, target_mechanisms→ the interferon node (ACTIVATES), TOGETHER-trial evidence (PMID:36780676). - Respiratory Syncytial Virus Infection — Nirsevimab (NCIT:C170224), a long-acting anti-RSV-F monoclonal antibody for passive immunoprophylaxis, target_mechanisms→ the epithelial-infection node (INHIBITS), MELODY-trial evidence (PMID:35235726).

Remaining wiring work: extend conforms_to/treatment edges to the rest of the core/endemic viruses as their entries grow (e.g. a dedicated influenza host- protease-cleavage entry node, an RSV interferon node), and add host-directed agents where clinically established.

Scope

In scope: infections whose primary disease is in the respiratory tract — upper (rhinitis/common cold, pharyngitis, sinusitis, laryngitis, croup, epiglottitis) and lower (bronchitis, bronchiolitis, pneumonia, empyema, lung abscess, pulmonary TB and fungal pneumonias). Systemic or zoonotic infections are in scope when a respiratory form is a principal manifestation (e.g. pneumonic plague, pneumonic tularemia, pulmonary glanders, varicella pneumonia), and post-acute respiratory sequelae (Long COVID).

Out of scope (cross-referenced, not owned here): - Non-infectious airway/parenchymal disease — Asthma, COPD, Hypersensitivity_Pneumonitis / Bird_Fanciers_Lung, Hereditary_Pulmonary_Alveolar_Proteinosis, Pulmonary_Hemosiderosis (these are immune/structural, not infections). - Structural/developmental lung disease — Congenital_Pulmonary_Airway_Malformation, Scimitar_Syndrome, Laryngotracheoesophageal_Cleft. - Host susceptibility entries (immunodeficiencies, Primary Ciliary Dyskinesia, Cystic Fibrosis) that predispose to recurrent respiratory infection — these belong to their own domains but are relevant comorbidity links.

Bronchiectasis is included as a boundary case: it is a chronic suppurative airway disease driven by a vicious cycle of infection and inflammation, often post-infectious, and is the structural endpoint many of these infections feed into.

Existing entries (seed set)

Viral

Bacterial / mycobacterial

Fungal

Coverage gaps (curation backlog)

High-value respiratory infections not yet in the KB, roughly priority-ordered. Items tagged [Intercept] broaden coverage of Intercept's endemic-respiratory-virus thesis (broad-spectrum protection across viral families) and are prioritized accordingly.

Endemic respiratory viruses [Intercept] — highest priority - Parainfluenza Virus Infection [Intercept] — ✓ created (de novo) - Middle East Respiratory Syndrome [Intercept] — ✓ created (de novo) - Human Metapneumovirus Infection [Intercept] — ✓ created (de novo; no MONDO disease_term — MONDO lacks an hMPV infection term, flagged for a term request). - Seasonal Coronavirus Infection [Intercept] — ✓ created (de novo; no MONDO disease_term — MONDO lacks an endemic-HCoV term, flagged for a term request). - Adenovirus Respiratory Infection [Intercept] — ✓ created (de novo; no MONDO disease_term — MONDO has only "adenovirus renal infection", flagged for a term request).

Bacterial pneumonia & atypicals - Chlamydophila pneumoniae (atypical pneumonia) - Haemophilus influenzae and Moraxella catarrhalis LRTI - Hospital-acquired / ventilator-associated pneumonia

Vaccine-preventable / classic URT & airway - Diphtheria - Acute bacterial/viral bronchitis - Acute sinusitis / rhinosinusitis - Streptococcal pharyngitis (as an entity distinct from Scarlet Fever) - Croup (laryngotracheobronchitis), epiglottitis

Fungal & opportunistic - Pneumocystis jirovecii pneumonia (PCP) - Pulmonary aspergillosis - Histoplasmosis - Blastomycosis - Pulmonary cryptococcosis

Workflow

1. Pick a gap entry above (or claim via the priority dashboard / /claim-disease).
2. Curate with /curate, anchoring pathophysiology on the host–pathogen interaction at the respiratory site.
3. Wire treatments to the appropriate drug-mechanism module(s) via target_mechanisms / conforms_to (see ANTIMICROBIAL / ANTIVIRAL / ANTIFUNGAL).
4. Validate: just validate <file>, just validate-kb-references <file>, just validate-terms <file>.

Intercept-aligned deepening track (core 4 already curated)

Beyond filling gaps, deepen the already-curated core viruses along Intercept's thesis:

• Wire the two new modules (host_directed_antiviral_dependency, innate_antiviral_interferon_response, both built) — add conforms_to edges from the core virus entries to the module conformance targets.
• Enrich broad-spectrum-preventative treatments on Influenza, COVID-19, Respiratory Syncytial Virus Infection, and Rhinovirus Infection — tag each with the right therapeutic_modality (VACCINE, MONOCLONAL_ANTIBODY, SIRNA, SMALL_MOLECULE) and wire via target_mechanisms (e.g. RSV nirsevimab + RSVpreF vaccine; influenza baloxavir cap-dependent-endonuclease inhibitor). 5. Add the new slug to the diseases: frontmatter list here.

Related

• ANTIMICROBIAL, ANTIVIRAL, ANTIFUNGAL — treatment-mechanism layer.
• COMORBIDITIES — respiratory-infection comorbidity/trajectory signals (e.g. RSV → asthma, influenza → bacterial superinfection).