Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1

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Fältnamn	Indikatorer	Metadata
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001		oai:DiVA.org:umu-227301
003		SwePub
008		240703s2024 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-2273012 URI
024	7	a https://doi.org/10.1038/s41467-024-49491-82 DOI
040		a (SwePub)umu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Dans, Madeline G.u Burnet Institute, VIC, Melbourne, Australia; Walter and Eliza Hall Institute, VIC, Parkville, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
245	1 0	a Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
264	1	b Springer Nature,c 2024
338		a electronic2 rdacarrier
520		a With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Infektionsmedicin0 (SwePub)302092 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Infectious Medicine0 (SwePub)302092 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
700	1	a Boulet, Coralieu Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland4 aut
700	1	a Watson, Gabrielle M.u Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Nguyen, Williamu Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Dziekan, Jerzy M.u Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Evelyn, Cindyu Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Reaksudsan, Kitsanapongu Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Mehra, Somyau Burnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia4 aut
700	1	a Razook, Zahrau Burnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia4 aut
700	1	a Geoghegan, Niall D.u Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Mlodzianoski, Michael J.u Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Goodman, Christopher Deanu School of Biosciences, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Ling, Dawson B.u Burnet Institute, VIC, Melbourne, Australia4 aut
700	1	a Jonsdottir, Thorey K.u Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden4 aut0 (Swepub:umu)thjo0151
700	1	a Tong, Joshuau Walter and Eliza Hall Institute, VIC, Parkville, Australia4 aut
700	1	a Famodimu, Mufuliat Toyinu Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom4 aut
700	1	a Kristan, Mojcau Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom4 aut
700	1	a Pollard, Harryu Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom4 aut
700	1	a Stewart, Lindsay B.u Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom4 aut
700	1	a Brandner-Garrod, Lukeu Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom4 aut
700	1	a Sutherland, Colin J.u Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom4 aut
700	1	a Delves, Michael J.u Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom4 aut
700	1	a McFadden, Geoffrey I.u School of Biosciences, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Barry, Alyssa E.u Burnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia4 aut
700	1	a Crabb, Brendan S.u Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia; Monash University, VIC, Melbourne, Australia4 aut
700	1	a de Koning-Ward, Tania F.u Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia4 aut
700	1	a Rogers, Kelly L.u Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Cowman, Alan F.u Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Tham, Wai-Hongu Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Sleebs, Brad E.u Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia4 aut
700	1	a Gilson, Paul R.u Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia4 aut
710	2	a Burnet Institute, VIC, Melbourne, Australia; Walter and Eliza Hall Institute, VIC, Parkville, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australiab Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland4 org
773	0	t Nature Communicationsd : Springer Natureg 15:1q 15:1x 2041-1723
856	4	u https://doi.org/10.1038/s41467-024-49491-8y Fulltext
856	4	u https://umu.diva-portal.org/smash/get/diva2:1881371/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-227301
856	4 8	u https://doi.org/10.1038/s41467-024-49491-8

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

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