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

Weston, Stuart; Coleman, Christopher; Haupt, Robert; Logue, James; Matthews, Krystal; Li, Yize; Reyes, Hanako; Weiss, Susan; Frieman, Matthew

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/). 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 urgently needed. 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 Middle East respiratory syndrome coronavirus (MERS-CoV). We found that 17 of these inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly followed up seven of these to demonstrate that all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found that both drugs protect mice from clinical disease.

Citation

Weston, S., Coleman, C., Haupt, R., Logue, J., Matthews, K., Li, Y., Reyes, H., Weiss, S., & Frieman, M. (2020). Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo. Journal of Virology, 94(21), Article e01218-20. https://doi.org/10.1128/JVI.01218-20

• Journal Article Type: Article
• Acceptance Date: Aug 14, 2020
• Online Publication Date: Aug 19, 2020
• Publication Date: Oct 14, 2020
• Deposit Date: Aug 8, 2022
• Print ISSN: 0022-538X
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 94
• Issue: 21
• Article Number: e01218-20
• DOI: https://doi.org/10.1128/JVI.01218-20
• Public URL: https://nottingham-repository.worktribe.com/output/9897716
• Publisher URL: https://journals.asm.org/doi/10.1128/JVI.01218-20