Repurposed drugs may have a speedier path to clinical use because they have already been shown to be safe in people. A study publishing May 19th in the open access journal PLOS Pathogens by Sandrine Belouzard and Jean Dubuisson at Pasteur Institute, Lille, France and colleagues suggests clofoctol may be an effective treatment for SARS-CoV-2 infections in mice.
While COVID-19 vaccines reduce hospitalizations and death, they do not control virus transmission, and affordable, effective therapies are needed. Previous attempts to repurpose medicines to treat COVID-19 patients have been unsuccessful. In order to identify potential antiviral therapies effective against COVID-19, authors accessed the Apteeus drug library, a collection of 1,942 approved drugs to identify molecules that exhibit antiviral activity against SARS-CoV-2. The authors selected clofoctol based on its antiviral potency and tested their hypothesis by testing its effects in SARS-CoV-2-infected mice.
The researchers found that transgenic mice treated with clofoctol had a decreased viral load, reduced inflammatory gene expression, and lowered pulmonary pathology. Future studies are needed to further understand the drug’s therapeutic potential in SARS-CoV-2 patients as the study was limited by the physiological differences between humans and mice. Additionally, the mice were sacrificed only two days after treatment, so longer-term effects remain unknown.
According to the authors, “The antiviral and anti-inflammatory properties of clofoctol, associated with its safety profile and unique pharmacokinetics make a strong case for proposing clofoctol as an affordable therapeutic candidate for the treatment of COVID-19 patients. Finally, the relatively low cost of this drug suggests that it is a potential clinical option for treatment of COVID-19 patients in resource-poor settings.”
“Antivirals targeting SARS-CoV-2 are sorely needed,” adds Dubuisson. “In this study, we screened a library of drug compounds and identified clofoctol as an antiviral against SARS-CoV-2. We further demonstrated that, in vivo, this compound reduces inflammatory gene expression and lowers pulmonary pathology and decreases viral load.”
In your coverage, please use this URL to provide access to the freely available article in PLOS Pathogens: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010498
Citation: Belouzard S, Machelart A, Sencio V, Vausselin T, Hoffmann E, Deboosere N, et al. (2022) Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice. PLoS Pathog 18(5): e1010498. https://doi.org/10.1371/journal.ppat.1010498
Author Countries: France
Funding: This work was supported by the Institut Pasteur de Lille (to JeD and BD), the Fondation pour la Recherche Médicale (FRM to JeD) and the Agence Nationale de la Recherche (ANR) (Project FRM_ANR Flash 20 ANTICOV to JeD), the Centre National de la Recherche Scientifique (CNRS: COVID and ViroCrib programs to JeD) and the I-SITE ULNE Foundation (I-Site_Covid20_ANTI-SARS2 to JeD) and the Conseil Régional Hauts-de-France (THERAPIDE grant N°20005467 to BD). We also received sponsor support from LVMH (to BD), fondation Rotary (to BD), Vinted (to BD), Crédit Mutuel Nord Europe (to BD), Entreprises et Cités (to BD), AG2R (to BD), DSD Système (to BD), M comme Mutuelle (to BD), Protecthoms (to BD), RBL Plastiques (to BD), Saverglass (to BD), Brasserie 3 Monts (to BD), Coron Art (to BD). EH received support from the I-SITE ULNE Foundation (ERC Generator Grant). The platform used in this work was supported by the European Union (ERC-STG INTRACELLTB grant 260901), the ANR (ANR-10-EQPX-04-01), the “Fonds Européen de Développement Régional” (Feder) (12001407 [D-AL] EquipEx ImagInEx BioMed), CPER-CTRL (Centre Transdisciplinaire de Recherche sur la Longévité) and the Région Hauts-de-France (convention 12000080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:European Patent Application Serial No. EP20305633.8, entitled “Compound and method for the treatment of coronaviruses” related to this work was filed on 10 June 2020. Authors TB, LB, CM, SB, PB, ND, BD, JeD, EH, AM, YR and TV of this manuscript are inventors of the patent.