Exploiting Natural Products-Based Therapeutics for Aflatoxin Mitigation

Aflatoxins B1 (AFB1) are fungal produced mycotoxins that are present in food supplies and are strongly associated with increased risk for thedevelopment of hepatocellular carcinoma. Currently, there are no known countermeasures to selectively mitigate AFB1 toxicity. To meet thischallenge, we successfully validated a Phase I proof-of-concept study to harness the microbiome extracts of scavenging mammals for bioactivenatural products as potential AFB1 countermeasures. We further coupled the selected extracts with transcriptome analysis to identifypotential drug targets and pathways that play important role in AFB1 toxicity. This information was used for in vitro screening of approveddrugs to discover their repurposed role as AFB1 countermeasures. In Phase II, we will expand our framework to purify and test the efficacy ofcompounds from identified bioactive extracts, as well as test these compounds and repurposed drugs in in vivo animal models. The finalPhase II outcome of this project will provide 1) in vivo validated efficacious natural products, and 2) a platform to repurpose known drugs forproviding rapid transition from bench to bedside for AFB1 countermeasures. This project represents a compelling opportunity to prevent thethreat associated with AFB1 induced toxicity that will benefit both public and military health.