Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19

Published on
Journal: Viruses
[저자] Meehyun Ko, So Young Chang, Soo Young Byun, Aleksandr Ianevski, Inhee Choi, Anne-Laure Pham Hung d’Alexandry d’Orengiani, Erlend Ravlo, Wei Wang, Magnar Bjørås, Denis E. Kainov, David Shum, Ji-Young Min, Marc P. Windisch
[Category] COVID-19, MERS, SARS,
PMC URL    [DOI] 10.3390/v13040651    
[Article Type] Article
[Source] PMC

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.

All Keywords
【저자키워드】 COVID-19, Drug repurposing, pandemic, drug combinations, FDA-approved drugs, Middle East respiratory syndrome Coronavirus, lung organoids, high-content screening, severe acute respiratory syndrome coronavirus disease, clinical isolate, 【초록키워드】 Corticosteroid, coronavirus disease, SARS-CoV-2, coronavirus, Remdesivir, drug, in vitro, MERS-CoV, effective drugs, infections, therapeutic, compounds, Korean, food, Combination, calu-3 cells, Middle East, therapeutic option, medical need, acute respiratory syndrome, FDA-approved drug, treat, South, viral life cycle, respiratory syndrome coronavirus, late stage, illnesses, VERO-E6, greater, tested, identify, United State, eight, screened, demonstrated, representing, Confirmed, selected drug, 【제목키워드】 drug, MERS-CoV, Screening, clinical, South Korea, option, isolate, Potential,