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

• Published in: Viruses Vol. 13; no. 4; p. 651
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.04.2021; MDPI
• Subjects: Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - pharmacology; Alanine - analogs & derivatives; Alanine - pharmacology; Animals; Antiviral Agents - pharmacology; Atovaquone; clinical isolate; Coronaviridae; Coronavirus Infections - virology; Coronaviruses; Corticosteroids; COVID-19; COVID-19 - drug therapy; Drug Approval; Drug Evaluation, Preclinical; Drug Repositioning; drug repurposing; Drug screening; Drug Synergism; Fatalities; FDA-approved drugs; high-content screening; Humans; Laboratories; Life Cycle Stages - drug effects; Life cycles; Middle East respiratory syndrome; Middle East respiratory syndrome coronavirus; Middle East Respiratory Syndrome Coronavirus - drug effects; Middle East Respiratory Syndrome Coronavirus - growth & development; Middle East Respiratory Syndrome Coronavirus - isolation & purification; Nelfinavir; Organoids; SARS-CoV-2 - drug effects; Severe acute respiratory syndrome coronavirus 2; severe acute respiratory syndrome coronavirus disease; Small Molecule Libraries - pharmacology; Middle East; Arabian Peninsula; South Korea; United States > US; Norway; COVID-19; FDA-approved drugs; clinical isolate; severe acute respiratory syndrome coronavirus disease; drug repurposing; Middle East respiratory syndrome coronavirus; lung organoids; pandemic; drug combinations; high-content screening
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13040651

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.