Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo

• Published in: bioRxiv
• Main Authors: Weston, Stuart, Coleman, Christopher M, Haupt, Rob, Logue, James, Matthews, Krystal, Frieman, Matthew
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.04.2020
• Subjects: Antiviral activity; Antiviral agents; Chloroquine; Coronaviruses; COVID-19; Cytotoxicity; Drug development; Drugs; FDA approval; Hydroxychloroquine; Pandemics; Severe acute respiratory syndrome coronavirus 2; Sulfates
• DOI: 10.1101/2020.03.25.008482

SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases and greater than 189,000 recorded deaths by April 23rd, 2020 (www.WHO.org). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs. Rapid development and human testing of potential antivirals is greatly needed. A quick way to test compounds with potential antiviral activity is through drug repurposing. Numerous drugs are already approved for human use and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV. We found that 17 of these also inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. We directly follow up with 7 of these to demonstrate all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we have evaluated two of these, chloroquine and chlorpromazine in vivo using a mouse-adapted SARS-CoV model and found both drugs protect mice from clinical disease. Competing Interest Statement The authors have declared no competing interest. Footnotes * The previous manuscript had the data that is in Fig 1 and had 2 independent repeats of the RNA and TCID50 experiments in Fig. 2. Those experiments in Fig. 2 now have three independent repeats. All other data in Fig. 2, 3 and 4 is new data added to the updated manuscript. As part of the data that has been added, two additional authors have been added in CMC and JMS.