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The recently discovered FREP1-mediated malaria transmission pathway is an excellent target to screen drugs for limiting transmission.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To identify candidate small molecules, we used an ELISA-based approach to analyze extracts from a fungal library for inhibition of the FREP1\u2013parasite interaction. We isolated and determined one active compound by chromatography and crystallography, respectively. We measured the effects of the bioactive compound on malaria transmission to mosquitoes through standard membrane-feeding assays (SMFA) and on parasite proliferation in blood by culturing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We discovered the ethyl acetate extract of the fungus <jats:italic>Purpureocillium lilacinum<\/jats:italic> that inhibited <jats:italic>Plasmodium falciparum<\/jats:italic> transmission to mosquitoes. Pre-exposure to the extract rendered <jats:italic>Anopheles gambiae<\/jats:italic> resistant to <jats:italic>Plasmodium<\/jats:italic> infection. Furthermore, we isolated one novel active compound from the extract and identified it as 3-amino-7,9-dihydroxy-1-methyl-6H-benzo[c]chromen-6-one, or \u201cpulixin.\u201d Pulixin prevented FREP1 from binding to <jats:italic>P. falciparum<\/jats:italic>-infected cell lysate. Pulixin blocked the transmission of the parasite to mosquitoes with an EC<jats:sub>50<\/jats:sub> (the concentration that gave half-maximal response)\u00a0of 11\u00a0\u00b5M based on SMFA. Notably, pulixin also inhibited the proliferation of asexual-stage <jats:italic>P. falciparum<\/jats:italic> with an EC<jats:sub>50<\/jats:sub> of 47\u00a0nM. The compound did not show cytotoxic effects at a concentration of 116\u00a0\u00b5M or lower.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>By targeting the FREP1\u2013<jats:italic>Plasmodium<\/jats:italic> interaction, we discovered that <jats:italic>Purpureocillium lilacinum<\/jats:italic> extract blocked malaria transmission. We isolated and identified the bioactive agent pulixin as a new compound capable of stopping malaria transmission to mosquitoes and inhibiting parasite proliferation in blood culture.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s13071-021-04677-7","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T20:07:57Z","timestamp":1616616477000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel fungal metabolite inhibits Plasmodium falciparum transmission and infection"],"prefix":"10.1186","volume":"14","author":[{"given":"Guodong","family":"Niu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shambhu","family":"Kandel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guomin","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael G.","family":"Raptis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"4677_CR1","unstructured":"WHO. 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