27Drug repositioning is the only feasible option to address the COVID-19 global challenge 28 immediately. We screened a panel of 48 FDA-approved drugs against SARS-CoV-2 which were 29 pre-selected by an assay of SARS-CoV and identified 24 potential antiviral drug candidates 30 against SARS-CoV-2 infection. Some drug candidates showed very low micromolar IC50s and 31 in particular, two FDA-approved drugs -niclosamide and ciclesonidewere notable in some 32 respects. 33 on June 9, 2020 by guest http://aac.asm.org/ Downloaded from 34 COVID-19 is an emerging infectious disease caused by a novel coronavirus, SARS-CoV-2 (1). 35Although the case fatality rate due to this viral infection varies from 1 to 12% (2), the 36 transmission rate is relatively high (3) and recently, the WHO declared COVID-19 outbreak a 37 pandemic. Currently, there is no vaccines or therapeutics available and the patients with COVID-38 19 are being treated with supportive care. 39Drug repositioning could be an effective strategy to respond immediately to emerging infectious 40 diseases since the new drug development usually takes more than 10 years (4). FDA-approved 41 drugs provide safe alternatives only in the case where at least modest antiviral activity can be 42 achieved. Accordingly, several drugs are being tested in numerous clinical trials (5) including 43 remdesivir, lopinavir, and chloroquine (6). 44In this study, we screened a panel of FDA-approved drugs to identify antiviral drug candidates 45 for the treatment of COVID-19 and suggest the identified drug candidates may be considered for 46 therapeutic development. 48 Results and Discussion 49We screened approximately 3,000 FDA-and IND-approved drug library against SARS-CoV to 50 identify antiviral drug candidates (manuscript in preparation). Since the SARS-CoV and SARS-51 CoV-2 are very similar (79.5% sequence identity) (1), the drugs which show antiviral activity 52 against SARS-CoV are expected to show similar extent of antiviral activity against SARS-CoV-2. 53A total of 35 drugs were selected from the earlier SARS-CoV screening results. In addition, 13 54 drugs were included based on recommendations from infectious diseases specialists (Table 1). 55For screening experiments, Vero cells were used and each drug was added to the cells prior to 56 the virus infection. At 24 h after the infection, the infected cells were scored by 57 immunofluorescence analysis with an antibody specific for the viral N protein of SARS-CoV-2. 58The confocal microscope images of both viral N protein and cell nuclei were analyzed using our 59 in-house Image Mining (IM) software and the dose-response curve (DRC) for each drug was 60 generated (Figure 1). 61 on June 9, 2020 by guest http://aac.asm.org/ Downloaded from Chloroquine, lopinavir, and remdesivir were used as reference drugs with IC 50 values of 9.12, 62 7.28, and 11.41 µM, respectively ( Figure 1A). Among the 48 drugs that were evaluated in our 63 study, 24 drugs showed potential antiviral activities against SARS-CoV-2 with IC 50 values in 64 be...

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Drug repositioning represents an effective way to control the current COVID‐19 pandemic. Previously, we identified 24 FDA‐approved drugs which exhibited substantial antiviral effect against severe acute respiratory syndrome coronavirus 2 in Vero cells. Since antiviral efficacy could be altered in different cell lines, we developed an antiviral screening assay with human lung cells, which is more appropriate than Vero cell. The comparative analysis of antiviral activities revealed that nafamostat is the most potent drug in human lung cells (IC 50 = 0.0022 µM).

AbstractCOVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50 < 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.

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-ofaddition 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.