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bioRxiv · 10.1101/2020.02.25.965582

Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19

Ko, M.·Chang, S. Y.·Byun, S. Y.·Choi, I.·d'Alexandry d'Orengiani, A. L. P. H.·Shum, D.·Min, J.-Y.·Windisch, M. P.
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Abstract

Therapeutic options for coronavirus remain limited. To address this unmet medical need, we screened 5,406 compounds, including United States Food and Drug Administration (FDA)- approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6. Time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI>100), atovaquone, an anti-malarial (TI>34), and ciclosonide, an inhalable corticosteroid (TI>6). Furthermore, utilizing the severe acute respiratory syndrome CoV-2 (SARS-CoV-2), combinations of remedesivir with selected dugs were evaluated, which identified ciclosonide and nelfinavir to be additive and synergistic drugs in vitro, respectively. Together, we screened FDA-approved drugs using patient-derived MERS-CoV, triaged hits to discriminate between early and late viral life cycle inhibitors, confirmed selected drugs using SARS-CoV-2, and demonstrated the added value of selected medications in combination with remedesivir. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.

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Ko, M., Chang, S. Y., Byun, S. Y., Choi, I., d'Alexandry d'Orengiani, A. L. P. H., Shum, D., Min, J.-Y., Windisch, M. P.. 2020-03-02. Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19. https://doi.org/10.1101/2020.02.25.965582

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