Daily Respiratory Research Analysis
Three impactful respiratory studies span antiviral discovery, diagnostic innovation, and mucosal immunology. A JCI study identifies HGS as a druggable host factor for pan-coronavirus assembly and proposes riboflavin tetrabutyrate as a repurposed inhibitor. Separately, dynamic chest radiography shows promise as a low-radiation alternative to PFTs for COPD screening, and Nature Communications reveals persistent neutrophilic nasal inflammation driving pneumococcal colonization in ART-treated HIV.
Summary
Three impactful respiratory studies span antiviral discovery, diagnostic innovation, and mucosal immunology. A JCI study identifies HGS as a druggable host factor for pan-coronavirus assembly and proposes riboflavin tetrabutyrate as a repurposed inhibitor. Separately, dynamic chest radiography shows promise as a low-radiation alternative to PFTs for COPD screening, and Nature Communications reveals persistent neutrophilic nasal inflammation driving pneumococcal colonization in ART-treated HIV.
Research Themes
- Host-targeted broad-spectrum antivirals for coronaviruses
- Imaging-based functional diagnostics for COPD
- Mucosal immune dysregulation and bacterial colonization in HIV
Selected Articles
1. Targeting the host factor HGS-viral membrane protein interaction in coronavirus infection.
A genome-wide CRISPRi screen identified HGS as essential for coronavirus assembly via direct interaction with the M protein, enabling ERGIC trafficking. HGS-targeting peptides and riboflavin tetrabutyrate disrupted this interaction, blocking virion assembly and demonstrating broad anti-coronavirus activity in vitro and in vivo.
Impact: This work reveals a conserved, druggable host-virus interface and provides a repurposed compound with in vivo efficacy, opening a host-directed antiviral modality with pandemic relevance.
Clinical Implications: Although preclinical, targeting HGS could yield broad-spectrum therapeutics less prone to resistance than viral protein inhibitors. Riboflavin tetrabutyrate merits pharmacokinetic/toxicity profiling and early-phase trials for coronavirus diseases.
Key Findings
- HGS directly binds coronavirus M protein to enable ERGIC trafficking and virion assembly; HGS deficiency retains M in ER and blocks assembly.
- M-derived peptides and riboflavin tetrabutyrate (RTB) bind HGS, disrupt HGS–M interaction, and prevent virion assembly.
- Agents targeting HGS demonstrated broad anti-pan-coronavirus activity in vitro and in vivo.
Methodological Strengths
- Genome-wide CRISPRi screening with mechanistic validation across in vitro and in vivo systems
- Large-scale drug repurposing screen (>5,000 FDA-approved compounds) plus rational peptide design
Limitations
- Preclinical study; human safety, pharmacokinetics, and optimal dosing are unknown
- Host-target engagement may entail on-target toxicity; off-target effects of RTB need evaluation
Future Directions: Advance RTB and peptide inhibitors into ADME/toxicology studies, assess efficacy in relevant animal disease models, and explore combination with direct-acting antivirals to mitigate resistance.
2. Dynamic Chest Radiography as an Alternative to Pulmonary Function Tests for Chronic Obstructive Pulmonary Disease.
In a prospective cohort of 553 participants, dynamic chest radiography metrics correlated with PFT indices among COPD patients. Predictive models built with LASSO-logistic regression achieved strong internal performance and yielded a calibrated nomogram, supporting DCR as a potential low-radiation alternative for COPD screening.
Impact: Offers a scalable, low-radiation, imaging-based functional assessment that could expand COPD screening where spirometry is limited.
Clinical Implications: DCR could triage patients for confirmatory PFTs, reduce barriers to COPD detection, and enable longitudinal monitoring where spirometry capacity is constrained.
Key Findings
- Among 553 participants, DCR parameters (e.g., bilateral ΔPLA during deep breathing) correlated with key PFT indices in COPD.
- LASSO-selected DCR features with multivariable logistic regression yielded strong ROC performance on an internal test set.
- A calibrated nomogram visualized COPD probability, supporting clinical interpretability.
Methodological Strengths
- Prospective design with relatively large sample size (n=553) and internal test set
- Multimethod evaluation including correlation analyses, ROC metrics, LASSO feature selection, and calibration
Limitations
- Single-center study with internal validation only; lacks external validation and head-to-head outcome studies
- Abstract truncation limits detailed reporting of specific AUC values and thresholds
Future Directions: Conduct external validation across diverse settings, assess cost-effectiveness and radiation dose optimization, and test DCR-enabled screening pathways on clinical outcomes.
3. Persistent pneumococcal colonisation in antiretroviral-treated HIV infection is associated with nasal inflammation.
ART-treated PLWH exhibit persistent epithelial-driven neutrophilic nasal inflammation with neutrophil senescence and T-cell exhaustion. This immune landscape correlates with higher pneumococcal carriage density, suggesting that targeting epithelial-immune crosstalk or neutrophil senescence could reduce pathogen burden.
Impact: Defines tissue-specific immune dysfunction under ART with mechanistic links to bacterial colonization, informing precision prevention strategies for respiratory infections in PLWH.
Clinical Implications: Beyond vaccination, interventions modulating epithelial chemokine signaling or reversing neutrophil senescence may complement strategies to reduce pneumococcal carriage and disease in PLWH on ART.
Key Findings
- Long-term ART does not restore nasal mucosal immunity: persistent epithelial-driven neutrophilic inflammation, T-cell exhaustion, and cellular senescence.
- Neutrophils show mitochondrial stress, SASP gene expression, and impaired oxidative burst, especially in pneumococcal carriers.
- Neutrophilic inflammation correlates strongly with pneumococcal carriage density, implying a feedforward loop sustaining colonization.
Methodological Strengths
- Multi-omic profiling combining flow cytometry, single-cell transcriptomics, and functional assays in primary human samples
- Direct linkage of immune phenotypes to quantitative colonization density
Limitations
- Observational design limits causal inference; sample size and ART regimen heterogeneity not detailed in abstract
- Generalizability may vary across geographies and microbiome contexts
Future Directions: Interventional studies targeting epithelial chemokines or neutrophil senescence pathways; longitudinal cohorts to test whether immune modulation reduces carriage and invasive disease.