Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19
Meehyun Ko, So Young Chang, Soo Young Byun, Inhee Choi, Anne Laure Pham Hung d'Alexandry d'Orengiani, David Shum, Ji-Young Min, Marc P. Windisch
doi: https://doi.org/10.1101/2020.02.25.965582
Abstract
In 2015, the Middle East respiratory syndrome coronavirus (MERS-CoV) reached the Republic of Korea, resulting from nosocomial transmission, and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, there are only limited therapeutic options available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including US Food and Drug Administration (FDA)-approved drugs and bioactive molecules, confirmed 221 hits by dose-response curve analysis in the primary assay, and selected 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that eight and four therapeutics act on the early- and late stages of the viral life cycle, respectively. Among the early acting drugs, three therapeutics with a TI greater than 100 were cardiotonic agents. Together, our results identify potential therapeutic options for treatment of MERS-CoV infections and could provide a basis for a wider range of coronaviruses, including the currently emerging coronavirus disease 2019 (COVID-19) outbreak.
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