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Cited by 247

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A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

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Madrid, Peter B., Chopra, Sidharth, Manger, Ian D., Gilfillan, Lynne, Keepers, Tiffany R., Shurtleff, Amy C., Green, Carol E., Iyer, Lalitha V., Dilks, Holli Hutcheson, Davey, Robert A., Kolokoltsov, Andrey A., Carrion, Ricardo, Patterson, Jean L., Bavari, Sina, Panchal, Rekha G., Warren, Travis K., Wells, Jay B., Moos, Walter H., Burke, RaeLyn L., Tanga, Mary J.·2013·PLoS ONE
DOI 10.1371/journal.pone.0060579
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Abstract

BACKGROUND: The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. METHODOLOGY/PRINCIPAL FINDINGS: A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. CONCLUSIONS/SIGNIFICANCE: The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses.

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Metadata

Authors
Madrid, P. B., Chopra, S., Manger, I. D., Gilfillan, L., Keepers, T. R., Shurtleff, A. C., Green, C. E., Iyer, L. V., Dilks, H. H., Davey, R. A., Kolokoltsov, A. A., Carrion, R., Patterson, J. L., Bavari, S., Panchal, R. G., Warren, T. K., Wells, J. B., Moos, W. H., Burke, R. L., & Tanga, M. J.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-04-05
Volume
8
Issue
4
Pages
e60579
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0060579
OpenAlex
W2146117672
Cited by
247
References
2
FWCI
10.76
Type
journal article
Language
en
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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CoChat. (2026). Citation check: A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents. https://app.cochat.ai/papers/10.1371/journal.pone.0060579
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Madrid, P. B., Chopra, S., Manger, I. D., Gilfillan, L., Keepers, T. R., Shurtleff, A. C., Green, C. E., Iyer, L. V., Dilks, H. H., Davey, R. A., Kolokoltsov, A. A., Carrion, R., Patterson, J. L., Bavari, S., Panchal, R. G., Warren, T. K., Wells, J. B., Moos, W. H., Burke, R. L., & Tanga, M. J. (2013). A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents. PLoS ONE. https://doi.org/10.1371/journal.pone.0060579

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