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In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication.
Touret, Franck; Gilles, Magali; Barral, Karine; Nougairède, Antoine; van Helden, Jacques; Decroly, Etienne; de Lamballerie, Xavier; Coutard, Bruno.
  • Touret F; Unité Des Virus Emergents (UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection), 13005, Marseille, France. franck.touret@univ-amu.fr.
  • Gilles M; Unité Des Virus Emergents (UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection), 13005, Marseille, France.
  • Barral K; Aix-Marseille Univ, INSERM U1068, CNRS UMR7258, Institut Paoli-Calmettes, CRCM, Marseille, France.
  • Nougairède A; Unité Des Virus Emergents (UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection), 13005, Marseille, France.
  • van Helden J; Institut Français de Bioinformatique (IFB), UMS 3601-CNRS, Université Paris-Saclay, Orsay, France.
  • Decroly E; Aix-Marseille Univ, INSERM, Lab. Theory and Approaches of Genome Complexity (TAGC), Marseille, France.
  • de Lamballerie X; AFMB UMR 7257, Aix-Marseille Université, CNRS, Marseille, France.
  • Coutard B; Unité Des Virus Emergents (UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection), 13005, Marseille, France.
Sci Rep ; 10(1): 13093, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-697117
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Small Molecule Libraries / Betacoronavirus Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Sci Rep Year: 2020 Document Type: Article Affiliation country: S41598-020-70143-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Small Molecule Libraries / Betacoronavirus Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Sci Rep Year: 2020 Document Type: Article Affiliation country: S41598-020-70143-6