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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.
David Shum.
Ji-Young Min.
Marc P. Windisch.
Acceso Abierto
In 2015, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) reached the Republic of Korea through nosocomial transmission and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, only limited therapeutic options are available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactive molecules, for their activity against the isolate. The primary assay confirmed 221 hits by dose-response curve analysis and identified 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that 8 and 4 therapeutics act on the early and late stages of the viral life cycle, respectively. Among the drugs were e.g., three cardiotonic agents (ouabain, digitoxin, digoxin) with a TI greater than 100, an anti-malaria drug (atovaquone; TI >34), an inhalable corticosteroid (ciclesonide; TI >6), etc. Together, our results identify potential therapeutic options for treating MERS-CoV infections and could provide a basis for agents against a wider range of coronavirus-related illnesses, including the currently emerging Coronavirus Disease 2019 (COVID-19) outbreak.
Appears in Collections:Artículos científicos

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