Kovi Bessoff, Microbiology & Molecular Genetics PhD Graduate student in Dr. Chris Huston’s lab, has published “Drug Repurposing Screen Reveals FDA-Approved Inhibitors of
Human HMG-CoA Reductase and Isoprenoid Synthesis that Block Cryptosporidium parvum Growth” in the journal Antimicrobial Agents and Chemotherapy.
“Cryptosporidiosis is a diarrheal disease with serious consequences in young children including chronic stunting, as well as in immunocompromised adults (especially people with AIDS),” said Mr. Bessoff, “Most human cases of cryptosporidiosis are caused by the parasites Cryptosporidium hominis or Cryptosporidium parvum, which are usually spread via contaminated water, making the disease a particularly severe problem in the developing world. Nitazoxanide, the current standard of care for the treatment of cryptosporidiosis is not effective in treating chronic infection in children or severe infection in AIDS patients. Unfortunately, technical difficulties associated with working with Cryptosporidium parasites in the laboratory, as well as the lack of financial incentives to discover new drugs against this mainly developing world problem have drastically hindered efforts to bring new anti-cryptosporidial drugs to the market. In an effort to circumvent these obstacles, we developed a system to screen candidate compounds for activity against Cryptosporidium parvum. We then utilized this system to screen a collection of 727 compounds that are either FDA approved or have a history of use in human clinic trials, meaning that they have demonstrated favorable safety profiles. Our recent publication outlines the development, optimization, and validation of the screening pipeline, and describes some of the drugs that we identified as repurposing candidates for the treatment of cryptosporidiosis, including itavastatin, which is an HMG-CoA reductase inhibitor that is traditionally used as a medicine to treat high cholesterol. Finally, through a combination of bioinformatic analysis and additional experiments, we were able to develop a model of how itavastatin might be working to inhibit the parasite.”
Congratulations on your publication, Kovi!