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Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo.
J Virol. 2020 10 14; 94(21)JV

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.

Authors+Show Affiliations

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA MFrieman@som.umaryland.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32817221

Citation

Weston, Stuart, et al. "Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs Against SARS-CoV-2 in Vitro and SARS-CoV in Vivo." Journal of Virology, vol. 94, no. 21, 2020.
Weston S, Coleman CM, Haupt R, et al. Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo. J Virol. 2020;94(21).
Weston, S., Coleman, C. M., Haupt, R., Logue, J., Matthews, K., Li, Y., Reyes, H. M., Weiss, S. R., & Frieman, M. B. (2020). Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo. Journal of Virology, 94(21). https://doi.org/10.1128/JVI.01218-20
Weston S, et al. Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs Against SARS-CoV-2 in Vitro and SARS-CoV in Vivo. J Virol. 2020 10 14;94(21) PubMed PMID: 32817221.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo. AU - Weston,Stuart, AU - Coleman,Christopher M, AU - Haupt,Robert, AU - Logue,James, AU - Matthews,Krystal, AU - Li,Yize, AU - Reyes,Hanako M, AU - Weiss,Susan R, AU - Frieman,Matthew B, Y1 - 2020/10/14/ PY - 2020/06/16/received PY - 2020/08/14/accepted PY - 2020/8/21/pubmed PY - 2020/10/28/medline PY - 2020/8/21/entrez KW - FDA-approved drugs KW - SARS-CoV-2 KW - antiviral therapeutics KW - coronavirus KW - drug repurposing KW - nCoV-2019 KW - pandemic JF - Journal of virology JO - J Virol VL - 94 IS - 21 N2 - 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. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/32817221/Broad_Anti_coronavirus_Activity_of_Food_and_Drug_Administration_Approved_Drugs_against_SARS_CoV_2_In_Vitro_and_SARS_CoV_In_Vivo_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=32817221 DB - PRIME DP - Unbound Medicine ER -