Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention
0301 basic medicine
Biological sciences
Cell biology
0303 health sciences
Virology
Science
Q
Pathology
Article
DOI:
10.1016/j.isci.2024.109191
Publication Date:
2024-02-13T17:26:43Z
AUTHORS (19)
ABSTRACT
The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free by C57BL/6 receiving oropharyngeal instillations a ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice COVID-19-like lung pathologies including ground-glass opacities, interstitial fibrosis, congested alveoli, became moribund. Lung tissues from these bronchoalveolar lavage patients showed elevated levels hyaluronic acid (HA), HA-family members, an inflammatory signature, immune cell infiltration. 4-methylumbelliferone (4-MU), oral drug for biliary-spasm treatment, inhibits HA-synthesis. At human equivalent dose, 4-MU prevented/inhibited long-term morbidity; metabolites accumulated lungs. Therefore, versatile pathology, HA as its critical mediator potential therapeutic COVID-19.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (61)
CITATIONS (1)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....