ArticleNature communications2021
Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53citing papers in PubMed
15.3field-weighted citation impact, top 1% of its field
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53 citing papers in PubMed, 92 citations in OpenAlex.
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- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of Plasmodium Phosphatidylinositol 4-Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria.Angewandte Chemie (International ed. in English) · 2025Article
- Screening the Pandemic Response Box identifies novel ligands of the Staphylococcus aureus protein arginine kinase, McsB.Molecular biology reports · 2025Article
- In vitro and in silico evaluation of synthetic compounds derived from bi-triazoles against asexual and sexual forms of Plasmodium falciparum.Malaria journal · 2025Article
- Eliminating malaria transmission requires targeting immature and mature gametocytes through lipoidal uptake of antimalarials.Nature communications · 2024Article
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- 2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors ofJournal of medicinal chemistry · 2024Article
- A pH Fingerprint Assay to Identify Inhibitors of Multiple Validated and Potential Antimalarial Drug Targets.ACS infectious diseases · 2024Article
- Genetic complexity alters drug susceptibility of asexual and gametocyte stages ofAntimicrobial agents and chemotherapy · 2024Article
- Identifying Fast and Slow-Acting Antimalarial Compounds of Pandemic Response Box Against Blood-Stage Culture of Plasmodium falciparum 3D7.Current microbiology · 2024Article
- Screening of the Pandemic Response Box identifies anti-microsporidia compounds.PLoS neglected tropical diseases · 2023Article
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Authors and funding
33 authors at 11 institutions in 4 countries.
Janette ReaderDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa.
Mariëtte E van der WattDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa.
Dale TaylorDrug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Claire Le ManachDrug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.ORCID 0000-0002-9310-0048
Nimisha MittalDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093-076, USA.
Sabine OttilieDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093-076, USA.
Anjo TheronNext Generation Health, Council for Scientific and Industrial Research, Pretoria, 0001, South Africa.ORCID 0000-0002-0497-4473
Phanankosi MoyoDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa.ORCID 0000-0001-7692-3256
Erica ErlankWits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, 2193, South Africa.
Luisa NardiniWits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, 2193, South Africa.ORCID 0000-0002-2438-5529
Nelius VenterWits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, 2193, South Africa.
Sonja LauterbachDepartment of Molecular Medicine and Hematology, Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.ORCID 0000-0003-4941-9972
Belinda BezuidenhoutDepartment of Molecular Medicine and Hematology, Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Andre HoratscheckDrug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.ORCID 0000-0001-6485-6391
Ashleigh van HeerdenDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa.ORCID 0000-0002-1081-4214
Natalie J SpillmanDivision of Infectious Diseases, Department of Medicine, Washington University, St. Louis, MO, 63110, USA.ORCID 0000-0002-3454-1636
Anne N CowellDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093-076, USA.
Jessica ConnacherDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa.
Daniel OppermanDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa.
Lindsey M OrchardDepartment of Biochemistry & Molecular Biology and the Huck Centre for Malaria Research, Pennsylvania State University, University Park, PA, 16802, USA.ORCID 0000-0003-1295-3733
Manuel LlinásDepartment of Biochemistry & Molecular Biology and the Huck Centre for Malaria Research, Pennsylvania State University, University Park, PA, 16802, USA.ORCID 0000-0002-6173-5882
Eva S IstvanDivision of Infectious Diseases, Department of Medicine, Washington University, St. Louis, MO, 63110, USA.ORCID 0000-0002-8666-3248
Daniel E GoldbergDivision of Infectious Diseases, Department of Medicine, Washington University, St. Louis, MO, 63110, USA.ORCID 0000-0003-3529-8399
Grant A BoyleDrug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
David CalvoGlobal Health Incubator Unit, GlaxoSmithKline (GSK), Severo Ochoa, 2, 28760, Tres Cantos, Madrid, Spain.ORCID 0000-0003-3551-2244
Dalu MancamaNext Generation Health, Council for Scientific and Industrial Research, Pretoria, 0001, South Africa.
Theresa L CoetzerDepartment of Molecular Medicine and Hematology, Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.ORCID 0000-0002-9467-1846
Elizabeth A WinzelerDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093-076, USA.ORCID 0000-0002-4049-2113
James DuffyMedicines for Malaria Venture, International Center Cointrin, Route de Pré-Bois 20, 1215, Geneva, Switzerland.
Lizette L KoekemoerWits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, 2193, South Africa.ORCID 0000-0003-4236-6345
Gregory BasarabDrug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.ORCID 0000-0001-5684-6046
Kelly ChibaleDrug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Lyn-Marié BirkholtzDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa. lbirkholtz@up.ac.za.ORCID 0000-0001-5888-2905
University of Pretoria · ZAUniversity of Cape Town · ZANational Health Laboratory Service · ZAUniversity of California San Diego · USUniversity of the Witwatersrand · ZAWashington University in St. Louis · USCouncil for Scientific and Industrial Research · ZAPennsylvania State University · USGlaxoSmithKline (Spain) · ESMedicines for Malaria Venture · CHSouth African Medical Research Council · ZA
Funding
Discovery of long-acting, chemoprotective antimalarial compoundsR01AI152533 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WINZELER, ELIZABETH A · 2020 to 2024
$3.5MNIAID NIH HHS R01 AI152533
Abstract
Chemical matter is needed to target the divergent biology associated with the different life cycle stages of Plasmodium. Here, we report the parallel de novo screening of the Medicines for Malaria Venture (MMV) Pandemic Response Box against Plasmodium asexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. Unique chemotypes were identified with both multistage activity or stage-specific activity, including structurally diverse gametocyte-targeted compounds with potent transmission-blocking activity, such as the JmjC inhibitor ML324 and the antitubercular clinical candidate SQ109. Mechanistic investigations prove that ML324 prevents histone demethylation, resulting in aberrant gene expression and death in gametocytes. Moreover, the selection of parasites resistant to SQ109 implicates the druggable V-type H
Indexed as
Drug DiscoveryPandemicsAedesAnimalsAntimalarialsCluster AnalysisDose-Response Relationship, DrugHep G2 CellsHumansInhibitory Concentration 50Life Cycle StagesLiverMalariaMalePlasmodium falciparumAntimalarials
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