Repurposing FDA approved drugs against the human fungal pathogen, Candida albicans
Kevin Kim, Leeor Zilbermintz, Mikhail Martchenko
Abstract
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Kevin Kim, Leeor Zilbermintz, Mikhail Martchenko
Abstract
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BACKGROUND: The high cost and prolonged timeline of new drug discovery and development are major roadblocks to creating therapies for infectious diseases. Candida albicans is an opportunistic fungal pathogen that is the most common cause of fatal fungal infections in humans and costs $2-4 billion dollars to treat in the US alone. METHODS: To accelerate drug discovery, we screened a library of 1581 existing FDA approved drugs, as well as drugs approved abroad, for inhibitors of C. albicans. The screen was done on YPD yeast growth media as well as on the serum plate assay developed in this study. RESULTS: We discovered that fifteen drugs, all which were originally approved for treating various infectious and non-infectious diseases, were able to kill Candida albicans. Additionally, one of those drugs, Octodrine, displays wide-spectrum anti-microbial activity. Compared to other selected anti-Candida drugs, Octodrine was shown to be one of the most effective drugs in killing serum-grown Candida albicans without significantly affecting the survival of host macrophages and skin cells. CONCLUSIONS: This approach is useful for the discovery of economically viable new therapies against infectious diseases.
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BACKGROUND: The high cost and prolonged timeline of new drug discovery and development are major roadblocks to creating therapies for infectious diseases. Candida albicans is an opportunistic fungal pathogen that is the most common cause of fatal fungal infections in humans and costs $2-4 billion dollars to treat in the US alone. METHODS: To accelerate drug discovery, we screened a library of 1581 existing FDA approved drugs, as well as drugs approved abroad, for inhibitors of C. albicans. The screen was done on YPD yeast growth media as well as on the serum plate assay developed in this study. RESULTS: We discovered that fifteen drugs, all which were originally approved for treating various infectious and non-infectious diseases, were able to kill Candida albicans. Additionally, one of those drugs, Octodrine, displays wide-spectrum anti-microbial activity. Compared to other selected anti-Candida drugs, Octodrine was shown to be one of the most effective drugs in killing serum-grown Candida albicans without significantly affecting the survival of host macrophages and skin cells. CONCLUSIONS: This approach is useful for the discovery of economically viable new therapies against infectious diseases.
Key concepts: Candida albicans, Repurposing, Drug repositioning, Fungal pathogen, Medical microbiology, Human pathogen, Approved drug, Biology