title: A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609.
abstract: Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine.
authors.forename: Rou
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis.
authors.forename: Rossarin
authors.initials: R
authors.lastname: Suwanarusk
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis.
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.affiliation: Department of Microbiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Cooke
authors.affiliation: Shoklo Malaria Research Unit, Mae Sot, Tak Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom.
authors.forename: Francois
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Yee-Ling
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge.
authors.forename: Ming
authors.initials: M
authors.lastname: Dao
authors.affiliation: Biomedical Engineering, National University of Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis.
authors.forename: Laurent
authors.initials: L
authors.lastname: Renia
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine.
authors.forename: Kevin Shyong Wei
authors.initials: KS
authors.lastname: Tan
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine.
authors.forename: Bruce
authors.initials: B
authors.lastname: Russell
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D010966:Plasmodium vivax / Q000187:drug effects* / Q000235:genetics; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D007211:Indoles; C552304:NITD 609; D013141:Spiro Compounds
keywords: KAE609; Plasmodium falciparum; Plasmodium vivax; malaria; red blood cell; spiroindolones