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

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 co...

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Autores principales: Belouzard, Sandrine, Machelart, Arnaud, Sencio, Valentin, Vausselin, Thibaut, Hoffmann, Eik, Deboosere, Nathalie, Rouillé, Yves, Desmarets, Lowiese, Séron, Karin, Danneels, Adeline, Robil, Cyril, Belloy, Loic, Moreau, Camille, Piveteau, Catherine, Biela, Alexandre, Vandeputte, Alexandre, Heumel, Séverine, Deruyter, Lucie, Dumont, Julie, Leroux, Florence, Engelmann, Ilka, Alidjinou, Enagnon Kazali, Hober, Didier, Brodin, Priscille, Beghyn, Terence, Trottein, François, Deprez, Benoit, Dubuisson, Jean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119441/
https://www.ncbi.nlm.nih.gov/pubmed/35587469
http://dx.doi.org/10.1371/journal.ppat.1010498
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author Belouzard, Sandrine
Machelart, Arnaud
Sencio, Valentin
Vausselin, Thibaut
Hoffmann, Eik
Deboosere, Nathalie
Rouillé, Yves
Desmarets, Lowiese
Séron, Karin
Danneels, Adeline
Robil, Cyril
Belloy, Loic
Moreau, Camille
Piveteau, Catherine
Biela, Alexandre
Vandeputte, Alexandre
Heumel, Séverine
Deruyter, Lucie
Dumont, Julie
Leroux, Florence
Engelmann, Ilka
Alidjinou, Enagnon Kazali
Hober, Didier
Brodin, Priscille
Beghyn, Terence
Trottein, François
Deprez, Benoit
Dubuisson, Jean
author_facet Belouzard, Sandrine
Machelart, Arnaud
Sencio, Valentin
Vausselin, Thibaut
Hoffmann, Eik
Deboosere, Nathalie
Rouillé, Yves
Desmarets, Lowiese
Séron, Karin
Danneels, Adeline
Robil, Cyril
Belloy, Loic
Moreau, Camille
Piveteau, Catherine
Biela, Alexandre
Vandeputte, Alexandre
Heumel, Séverine
Deruyter, Lucie
Dumont, Julie
Leroux, Florence
Engelmann, Ilka
Alidjinou, Enagnon Kazali
Hober, Didier
Brodin, Priscille
Beghyn, Terence
Trottein, François
Deprez, Benoit
Dubuisson, Jean
author_sort Belouzard, Sandrine
collection PubMed
description 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 IC(50) 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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spelling pubmed-91194412022-05-20 Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice Belouzard, Sandrine Machelart, Arnaud Sencio, Valentin Vausselin, Thibaut Hoffmann, Eik Deboosere, Nathalie Rouillé, Yves Desmarets, Lowiese Séron, Karin Danneels, Adeline Robil, Cyril Belloy, Loic Moreau, Camille Piveteau, Catherine Biela, Alexandre Vandeputte, Alexandre Heumel, Séverine Deruyter, Lucie Dumont, Julie Leroux, Florence Engelmann, Ilka Alidjinou, Enagnon Kazali Hober, Didier Brodin, Priscille Beghyn, Terence Trottein, François Deprez, Benoit Dubuisson, Jean PLoS Pathog Research Article 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 IC(50) 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. Public Library of Science 2022-05-19 /pmc/articles/PMC9119441/ /pubmed/35587469 http://dx.doi.org/10.1371/journal.ppat.1010498 Text en © 2022 Belouzard et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Belouzard, Sandrine
Machelart, Arnaud
Sencio, Valentin
Vausselin, Thibaut
Hoffmann, Eik
Deboosere, Nathalie
Rouillé, Yves
Desmarets, Lowiese
Séron, Karin
Danneels, Adeline
Robil, Cyril
Belloy, Loic
Moreau, Camille
Piveteau, Catherine
Biela, Alexandre
Vandeputte, Alexandre
Heumel, Séverine
Deruyter, Lucie
Dumont, Julie
Leroux, Florence
Engelmann, Ilka
Alidjinou, Enagnon Kazali
Hober, Didier
Brodin, Priscille
Beghyn, Terence
Trottein, François
Deprez, Benoit
Dubuisson, Jean
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
title_full Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice
title_fullStr Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice
title_full_unstemmed Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice
title_short Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice
title_sort clofoctol inhibits sars-cov-2 replication and reduces lung pathology in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119441/
https://www.ncbi.nlm.nih.gov/pubmed/35587469
http://dx.doi.org/10.1371/journal.ppat.1010498
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