Systematic repurposing of drugs as medical countermeasures to chemical threats

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.