Dataset Information

A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.

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.

SUBMITTER: Madrid PB

PROVIDER: S-EPMC3618516 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.

Madrid Peter B PB Chopra Sidharth S Manger Ian D ID Gilfillan Lynne L Keepers Tiffany R TR Shurtleff Amy C AC Green Carol E CE Iyer Lalitha V LV Dilks Holli Hutcheson HH Davey Robert A RA Kolokoltsov Andrey A AA Carrion Ricardo R Patterson Jean L JL Bavari Sina S Panchal Rekha G RG Warren Travis K TK Wells Jay B JB Moos Walter H WH Burke Raelyn L RL Tanga Mary J MJ

PloS one 20130405 4

<h4>Background</h4>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 indi ...[more]

PMID: 23577127

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Dataset Information

A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.

Background

Methodology/principal findings

Conclusions/significance

Publications

A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.

Similar Datasets

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