Pulmonary delivery of clofoctol-loaded nanoparticles inhibits SARS-CoV-2 replication and reduces pneumonia
Abstract
Despite the progress made through vaccination campaigns and the use of antivirals, the need for more effective therapeutics to combat respiratory viral infections remains critical. A recent screening of over 2000 repurposed molecules has identified the antibiotic clofoctol (CFT) as a promising candidate for treating COVID-19. However, administering CFT systemically poses challenges due to its low solubility and potential toxicity. In this study, we engineered poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles (NPs) designed to encapsulate high payloads of CFT, allowing for a controlled drug release in the pulmonary environment. Pharmacokinetic studies demonstrated high CFT bioavailability 8 h after intranasal (i.n.) administration. In preclinical models (mouse and hamster) of COVID-19, i.n. administration of CFT-loaded NPs significantly reduced pulmonary viral loads. Remarkably, vectorized CFT also decreased inflammation and improved pathological scores in the lungs. These results pave the way for a groundbreaking CFT formulation designed to tackle the challenges posed by acute respiratory infections. This study marks the first demonstration of a stable, effective and well-tolerated CFT formulation for the treatment of lung diseases.
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BibTeX
@article{bourguignon2026pulmonary,
title = {{Pulmonary delivery of clofoctol-loaded nanoparticles inhibits SARS-CoV-2 replication and reduces pneumonia}},
author = {Tom Bourguignon and Jesus Alfredo Godinez-Leon and Amine Pochet and Tahmida Shamsuddin and Valentin Sencio and Jonathan Chatagnon and Axelle Grandé and Joan Fine and Séverine Heumel and Cyril Robil and Lou Delval and Catherine Piveteau and Sandrine Belouzard and Priscille Brodin and François Trottein and Arnaud Machelart and Ruxandra Gref},
journal = {International Journal of Pharmaceutics},
year = {2026},
month = oct,
doi = {10.1016/j.ijpharm.2025.125634},
url = {https://hal.science/hal-05805890v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pulmonary delivery of clofoctol-loaded nanoparticles inhibits SARS-CoV-2 replication and reduces pneumonia
AU - Tom Bourguignon
AU - Jesus Alfredo Godinez-Leon
AU - Amine Pochet
AU - Tahmida Shamsuddin
AU - Valentin Sencio
AU - Jonathan Chatagnon
AU - Axelle Grandé
AU - Joan Fine
AU - Séverine Heumel
AU - Cyril Robil
AU - Lou Delval
AU - Catherine Piveteau
AU - Sandrine Belouzard
AU - Priscille Brodin
AU - François Trottein
AU - Arnaud Machelart
AU - Ruxandra Gref
PY - 2026
DA - 2026/10/19
JO - International Journal of Pharmaceutics
DO - 10.1016/j.ijpharm.2025.125634
UR - https://hal.science/hal-05805890v1
AB - Despite the progress made through vaccination campaigns and the use of antivirals, the need for more effective therapeutics to combat respiratory viral infections remains critical. A recent screening of over 2000 repurposed molecules has identified the antibiotic clofoctol (CFT) as a promising candidate for treating COVID-19. However, administering CFT systemically poses challenges due to its low solubility and potential toxicity. In this study, we engineered poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles (NPs) designed to encapsulate high payloads of CFT, allowing for a controlled drug release in the pulmonary environment. Pharmacokinetic studies demonstrated high CFT bioavailability 8 h after intranasal (i.n.) administration. In preclinical models (mouse and hamster) of COVID-19, i.n. administration of CFT-loaded NPs significantly reduced pulmonary viral loads. Remarkably, vectorized CFT also decreased inflammation and improved pathological scores in the lungs. These results pave the way for a groundbreaking CFT formulation designed to tackle the challenges posed by acute respiratory infections. This study marks the first demonstration of a stable, effective and well-tolerated CFT formulation for the treatment of lung diseases.
SN - 0378-5173
ER -