FDA approved drugs with broad anti-coronaviral activity inhibit SARS-CoV-2 in vitro

Stuart Weston; Rob Haupt; James Logue; Krystal Matthews; Matthew B. Frieman

The SARS-CoV-2 pandemic has demonstrated the need for antiviral drugs with broad activity against a range of viruses. Whether treating SARS-CoV-2 in this current pandemic or the next unknown viral pathogen, we must attempt to have validated antiviral drugs that are ready at the first signs of an outbreak. Many FDA approved drugs have been found to have antiviral activity and since these are extensively used in humans for other conditions, they could be streamlined for rapid approval for alternative use as antivirals. We previously performed a screen of 290 FDA approved drugs and found a subset of these to have antiviral activity against SARS-CoV and MERS-CoV (4). We prioritized testing these for antiviral activity against SARS-CoV-2. From multiple independent screens performed with two MOI, we found that 17 of our 20 tested compounds display significant antiviral activity at non-cytotoxic concentrations. Many of the compounds have IC50 values under 10µM and these will be the source of follow up testing on additional cell lines and in mouse models of SARS-CoV-2. We have further tested . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.008482 doi: bioRxiv preprint hydroxychloroquine and chloroquine phosphate for antiviral activity at the level of inhibiting viral mRNA (using N and RdRp) and infectious viral particle production (measured by TCID50 assay). Both drugs showed inhibitory properties, but hydroxychloroquine had greater antiviral activity. These data should be used to inform future planned human to assess antiviral activity of chloroquine or derivative drugs. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.008482 doi: bioRxiv preprint change for drug treated to vehicle control was calculated (dotted line to denote a fold change of 1 which is no change over control). Data are from 2 independent infections performed on triplicate wells, the fold change was calculated in each independent experiment and the mean fold change is plotted with error bars displaying standard deviation. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.008482 doi: bioRxiv preprint . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.008482 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.008482 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.008482 doi: bioRxiv preprint