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

• Published in: PLoS pathogens Vol. 18; no. 5; p. e1010498
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 19.05.2022; Public Library of Science (PLoS)
• Subjects: ACE2; Angiotensin-converting enzyme 2; Antibiotics; Antiviral activity; Antiviral drugs; Cell culture; Coronaviruses; COVID-19; COVID-19 vaccines; Cytotoxicity; Disease transmission; Drug dosages; Experiments; Gene expression; Infections; Inflammation; Life Sciences; Lungs; Microbiology and Parasitology; Pathology; Pharmaceutical research; Pharmacokinetics; Respiratory tract; Respiratory tract diseases; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Testing; Transgenic mice; Virology; France
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1010498

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.