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    Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 and SARS-CoV

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    Author
    Weston, Stuart
    Coleman, Christopher M
    Haupt, Robert
    Logue, James
    Matthews, Krystal
    Li, Yize
    Reyes, Hanako M
    Weiss, Susan R
    Frieman, Matthew B
    Date
    2020-10-14
    Journal
    Journal of Virology
    Publisher
    American Society for Microbiology
    Type
    Article
    Other
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1128/JVI.01218-20
    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.IMPORTANCE There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.
    Rights/Terms
    Copyright © 2020 American Society for Microbiology.
    Keyword
    FDA-approved drugs
    SARS-CoV-2
    antiviral therapeutics
    coronavirus
    drug repurposing
    nCoV-2019
    pandemic
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13983
    ae974a485f413a2113503eed53cd6c53
    10.1128/JVI.01218-20
    Scopus Count
    Collections
    UMB Coronavirus Publications
    UMB Open Access Articles

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