{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:04:37Z","timestamp":1782281077328,"version":"3.54.5"},"posted":{"date-parts":[[2025,1,3]]},"group-title":"Microbiology","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Cryptosporidium<\/jats:italic>\n                  is a common, waterborne gastrointestinal parasite that causes diarrheal disease worldwide. Currently there are no effective therapeutics to treat cryptosporidiosis in at-risk populations. Since natural products are a known source of anti-parasitic compounds, we screened a library of extracts and pure natural product compounds isolated from bacteria and fungi collected from subterranean environments for activity against\n                  <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                  . Eight structurally related norditerpene lactones isolated from the fungus\n                  <jats:italic>Oidiodendron truncatum<\/jats:italic>\n                  collected from the Soudan Iron mine in Minnesota showed potent activity and were further tested to identify the most active compounds. The availability of a diverse suite of natural structural analogs with varying activities allowed us to determine some structure activity relationships for both anti-parasitic activity as well as cytotoxicity. The two most potent compounds, oidiolactones A and B, had EC\n                  <jats:sub>50<\/jats:sub>\n                  s against intracellular\n                  <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                  of 530 and 240 nM respectively without cytotoxicity to confluent HCT-8 host cells. Both compounds also inhibited the related parasite\n                  <jats:italic>Toxoplasma gondii<\/jats:italic>\n                  . Oidiolactone A was active against asexual, but not sexual, stages of\n                  <jats:italic>C. parvum<\/jats:italic>\n                  , and killed 80% of the parasites within 8 hours of treatment. This compound reduced\n                  <jats:italic>C. parvum<\/jats:italic>\n                  infection by 70% in IFN\u03b3\u2212\/\u2212 mice, with no signs of toxicity. The high potency, low cytotoxicity, and\n                  <jats:italic>in vivo<\/jats:italic>\n                  activity combined with high production, easy isolation from fungi, and synthetic accessibility make oidiolactones A and B attractive scaffolds for the development of new anti-\n                  <jats:italic>Cryptosporidium<\/jats:italic>\n                  therapeutics.\n                <\/jats:p>","DOI":"10.1101\/2025.01.02.631097","type":"posted-content","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T07:30:23Z","timestamp":1735889423000},"source":"Crossref","is-referenced-by-count":0,"title":["Norditerpene natural products from subterranean fungi with anti-parasitic activity"],"prefix":"10.64898","author":[{"given":"Alexandra","family":"Kolas","sequence":"first","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA 55108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudi","family":"Rusman","sequence":"additional","affiliation":[{"name":"Center for Drug Design, University of Minnesota, Minnesota, USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.G.","family":"Maia","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA 55108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Drug Design, University of Minnesota, Minnesota, USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda G.","family":"Fumuso","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA 55108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Cotto-Rosario","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA 55108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chidiebere","family":"Onoh","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA 55108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanen","family":"Baggar","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA 55108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Piaskowski","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, USA 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Central Florida, 12722 Research Parkway, Orlando, Florida 32826, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyssa","family":"Weible","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2007-2170","authenticated-orcid":false,"given":"Kayode K.","family":"Ojo","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2757-754X","authenticated-orcid":false,"given":"Roberta 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