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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17 18 A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly 19 spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing 21 of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this 22 study, we screened the Prestwick Chemical Library® composed of 1,520 approved drugs in an infected 23 cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the 24 identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. 25The hits were sorted according to their chemical composition and their known therapeutic effect, then 26 EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, 27 Opipramol, Quinidine or Omeprazol present antiviral potency with 2