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Publication : Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice.

First Author  Belouzard S Year  2022
Journal  PLoS Pathog Volume  18
Issue  5 Pages  e1010498
PubMed ID  35587469 Mgi Jnum  J:335948
Mgi Id  MGI:7283486 Doi  10.1371/journal.ppat.1010498
Citation  Belouzard S, et al. (2022) Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice. PLoS Pathog 18(5):e1010498
abstractText  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.
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