Academic Journal
Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice.
| Title: | Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice. |
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| Authors: | Sandrine Belouzard, Arnaud Machelart, Valentin Sencio, Thibaut Vausselin, Eik Hoffmann, Nathalie Deboosere, Yves Rouillé, Lowiese Desmarets, Karin Séron, Adeline Danneels, Cyril Robil, Loic Belloy, Camille Moreau, Catherine Piveteau, Alexandre Biela, Alexandre Vandeputte, Séverine Heumel, Lucie Deruyter, Julie Dumont, Florence Leroux, Ilka Engelmann, Enagnon Kazali Alidjinou, Didier Hober, Priscille Brodin, Terence Beghyn, François Trottein, Benoit Deprez, Jean Dubuisson |
| Source: | PLoS Pathogens, Vol 18, Iss 5, p e1010498 (2022) |
| Publisher Information: | Public Library of Science (PLoS), 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| Subject Terms: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| More Details: | Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to its favorable safety profile and pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC50 measured against SARS-CoV-2 in human pulmonary cells. This compound inhibits SARS-CoV-2 at a post-entry step. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and lowered pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7366 1553-7374 87060787 |
| Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1010498 |
| Access URL: | https://doaj.org/article/ef24a1fe221949deb66833f87060787b |
| Accession Number: | edsdoj.f24a1fe221949deb66833f87060787b |
| Database: | Directory of Open Access Journals |
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| ISSN: | 15537366 15537374 87060787 |
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| DOI: | 10.1371/journal.ppat.1010498 |
| Published in: | PLoS Pathogens |
| Language: | English |