1. Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19.
- Author
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Ko, Meehyun, Chang, So Young, Byun, Soo Young, Ianevski, Aleksandr, Choi, Inhee, Pham Hung d'Alexandry d'Orengiani, Anne-Laure, Ravlo, Erlend, Wang, Wei, Bjørås, Magnar, Kainov, Denis E., Shum, David, Min, Ji-Young, Windisch, Marc P., Lundstrom, Kenneth, and Aljabali, Alaa A. A.
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COVID-19 , *MERS coronavirus , *SARS disease , *MIDDLE East respiratory syndrome , *ANTIMALARIALS - Abstract
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 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, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which 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 ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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