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In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication

Abstract : A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.
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Submitted on : Monday, September 21, 2020 - 3:16:07 PM
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Franck Touret, Magali Gilles, Karine Barral, Antoine Nougairède, Jacques van Helden, et al.. In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication. Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.13093. ⟨10.1038/s41598-020-70143-6⟩. ⟨inserm-02944556⟩



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