TY - JOUR
T1 - Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice
AU - Belouzard, Sandrine
AU - Machelart, Arnaud
AU - Sencio, Valentin
AU - Vausselin, Thibaut
AU - Hoffmann, Eik
AU - Deboosere, Nathalie
AU - Rouillé, Yves
AU - Desmarets, Lowiese
AU - Séron, Karin
AU - Danneels, Adeline
AU - Robil, Cyril
AU - Belloy, Loic
AU - Moreau, Camille
AU - Piveteau, Catherine
AU - Biela, Alexandre
AU - Vandeputte, Alexandre
AU - Heumel, Séverine
AU - Deruyter, Lucie
AU - Dumont, Julie
AU - Leroux, Florence
AU - Engelmann, Ilka
AU - Alidjinou, Enagnon Kazali
AU - Hober, Didier
AU - Brodin, Priscille
AU - Beghyn, Terence
AU - Trottein, François
AU - Deprez, Benoit
AU - Dubuisson, Jean
N1 - Publisher Copyright:
Copyright: © 2022 Belouzard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85130766389
U2 - 10.1371/journal.ppat.1010498
DO - 10.1371/journal.ppat.1010498
M3 - Article
C2 - 35587469
AN - SCOPUS:85130766389
SN - 1553-7366
VL - 18
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 5
M1 - e1010498
ER -