tetano
Editor, Senior Moderator
J Virol
. 2020 Aug 19;JVI.01218-20.
doi: 10.1128/JVI.01218-20. Online ahead of print.
Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo
Stuart Weston[SUP] 1 [/SUP], Christopher M Coleman[SUP] 1 [/SUP], Robert Haupt[SUP] 1 [/SUP], James Logue[SUP] 1 [/SUP], Krystal Matthews[SUP] 1 [/SUP], Yize Li[SUP] 2 [/SUP], Hanako M Reyes[SUP] 2 [/SUP], Susan R Weiss[SUP] 2 [/SUP], Matthew B Frieman[SUP] 3 [/SUP]
Affiliations
Abstract
SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with over 20 million recorded COVID-19 cases in August 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. 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 inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly follow up with seven 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.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 re-purposed 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 find 17 of these inhibit SARS-CoV-2, suggesting these may have pan-anti-coronaviral activity. We directly follow-up with seven of these and find they all inhibit infectious SARS-CoV-2 production. Moreover, we have evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We find neither drug inhibited viral replication in the lungs, but both protected against clinical disease.
. 2020 Aug 19;JVI.01218-20.
doi: 10.1128/JVI.01218-20. Online ahead of print.
Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo
Stuart Weston[SUP] 1 [/SUP], Christopher M Coleman[SUP] 1 [/SUP], Robert Haupt[SUP] 1 [/SUP], James Logue[SUP] 1 [/SUP], Krystal Matthews[SUP] 1 [/SUP], Yize Li[SUP] 2 [/SUP], Hanako M Reyes[SUP] 2 [/SUP], Susan R Weiss[SUP] 2 [/SUP], Matthew B Frieman[SUP] 3 [/SUP]
Affiliations
- PMID: 32817221
- DOI: 10.1128/JVI.01218-20
Abstract
SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with over 20 million recorded COVID-19 cases in August 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. 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 inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly follow up with seven 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.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 re-purposed 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 find 17 of these inhibit SARS-CoV-2, suggesting these may have pan-anti-coronaviral activity. We directly follow-up with seven of these and find they all inhibit infectious SARS-CoV-2 production. Moreover, we have evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We find neither drug inhibited viral replication in the lungs, but both protected against clinical disease.