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      Systematic repurposing of drugs as medical countermeasures to chemical threats

      Published
      conference-abstract
      1 , 1 , 1 , 1 , 2 , 1
      REPO4EU
      RExPO23
      25-26 October 2023
      drug development, medical countermeasures, SM and Ch-triggered injuries, machine learning
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            Abstract

            Accidental exposure to or attack by chemicals can trigger both acute and long-term adverse health effects. Fast intervention and decision making by first responders is critical, and accurate drug administration is needed. However, there are currently no FDA-approved drugs to treat effects of exposure to chlorine gas (Ch) or sulfur mustard (SM).

            To tackle this gap, BARDA (Biomedical Advanced Research and Development Authority) collaborated with Clarivate to computationally identify commonly available therapeutics that can be used by first responders as medical countermeasures (MCMs) to treat SM and Ch-triggered injuries.

            We first prioritized targets to be repurposed by combining publicly available transcriptomics datasets of exposure to chemicals with computational pipelines integrating machine learning, Systems Biology approaches and manually curated network and drug development intelligence databases.

            Subsequent manual drug factor analysis of top ranked candidate targets provided evidence (including efficacy, side effects, administration type, feasibility of large-scale stockpiling) to classify associated drugs into high, medium, and low priority categories for repositioning.

            Top-ranked drugs included inflammasome inhibitors, thrombopoietin receptor agonists and matrix metalloproteinase inhibitors, addressing both acute and long-term effects of hematological and pulmonary damages upon exposure to SM and Ch.

            Content

            Author and article information

            Conference
            REPO4EU
            9 October 2023
            Affiliations
            [1 ] Clarivate ( https://ror.org/04fce1c40)
            [2 ] Clarivate;
            Article
            10.58647/REXPO.23031
            3a55c02c-9c13-4426-a435-33d8018c5947
            Authors

            Published under Creative Commons Attribution 4.0 International ( CC BY 4.0). Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source.

            RExPO23
            2
            Stockholm, Sweden
            25-26 October 2023
            History
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            REPO4EU

            Categories

            Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
            Pharmacology & Pharmaceutical medicine
            drug development,medical countermeasures,SM and Ch-triggered injuries,machine learning

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