Abstract
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 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.
Summary Antivirals targeting SARS-CoV-2 are sorely needed. 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.
Competing Interest Statement
T.B., L.B., C.M., S.B., P.B., N.D., B.D., Je.D., E.H., A.M., Y.R., T.V. are inventors on a patent application on repurposed antiviral activity of clofoctol against SARS-CoV-2 owned by Univ Lille, CNRS, INSERM, CHU Lille and Institut Pasteur de Lille. European Patent Application Serial No. EP20305633.8, entitled Compound and method for the treatment of coronaviruses, relates to this work and was filed on 10 June 2020. The Institut Pasteur de Lille received a financial support from the group LVMH to help launching a clinical trial with clofoctol