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With the loss of antimalarials to resistance, the malaria burden will likely continue for decades. New antimalarial scaffolds are crucial to avoid cross-resistance. Here, we present the first structure based virtual screening using the \u03b2-haematin crystal as a target for new inhibitor scaffolds by applying a docking method. The ZINC15 database was searched for compounds with high binding affinity with the surface of the \u03b2-haematin crystal using the PyRx Virtual Screening Tool. Top-ranked compounds predicted to interact with \u03b2-haematin were submitted to a second screen applying<jats:italic>in silico<\/jats:italic>toxicity and drug-likeness predictions using Osiris DataWarrior. Fifteen compounds were purchased for experimental testing. An NP-40 mediated \u03b2-haematin inhibition assay and parasite growth inhibition activity assay were performed. The benzoxazole moiety was found to be a promising scaffold for further development, showing intraparasitic haemozoin inhibition using a cellular haem fractionation assay causing a decrease in haemozoin in a dose dependent manner with a corresponding increase in exchangeable haem. A \u03b2-haematin inhibition hit rate of 73% was found, a large enrichment over random screening, demonstrating that virtual screening can be a useful and cost-effective approach in the search for new haemozoin inhibiting antimalarials.<\/jats:p>","DOI":"10.1038\/s41598-020-60221-0","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T11:03:07Z","timestamp":1582628587000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Virtual screening as a tool to discover new \u03b2-haematin inhibitors with activity against malaria parasites"],"prefix":"10.1038","volume":"10","author":[{"given":"Ana Carolina C.","family":"de Sousa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Combrinck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keletso","family":"Maepa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Egan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"key":"60221_CR1","unstructured":"WHO. 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