dekoning-targetingmalaria-2019.pdf (2.27 MB)
Targeting malaria parasite invasion of red blood cells as an antimalarial strategy
journal contribution
posted on 2019-05-01, 00:00 authored by Amy L Burns, Madeline G Dans, Juan M Balbin, Tania De Koning-WardTania De Koning-Ward, Paul R Gilson, James G Beeson, Michelle J Boyle, Danny W WilsonPlasmodium spp. parasites that cause malaria disease remain a significant global-health burden. With the spread of parasites resistant to artemisinin combination therapies in Southeast Asia, there is a growing need to develop new antimalarials with novel targets. Invasion of the red blood cell by Plasmodium merozoites is essential for parasite survival and proliferation, thus representing an attractive target for therapeutic development. Red blood cell invasion requires a co-ordinated series of protein/protein interactions, protease cleavage events, intracellular signals, organelle release and engagement of an actin-myosin motor, which provide many potential targets for drug development. As these steps occur in the bloodstream, they are directly susceptible and exposed to drugs. A number of invasion inhibitors against a diverse range of parasite proteins involved in these different processes of invasion have been identified, with several showing potential to be optimised for improved drug-like properties. In this review, we discuss red blood cell invasion as a drug target and highlight a number of approaches for developing antimalarials with invasion inhibitory activity to use in future combination therapies.
History
Journal
FEMS microbiology reviewsVolume
43Issue
3Pagination
223 - 238Publisher
Oxford University PressLocation
Oxford, Eng.Publisher DOI
ISSN
0168-6445eISSN
1574-6976Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2019, FEMSUsage metrics
Categories
Keywords
P. falciparumP. vivaxantimalarial(s)invasionmalariamerozoitesScience & TechnologyLife Sciences & BiomedicineMicrobiologyDEPENDENT PROTEIN-KINASEMEROZOITE SURFACE PROTEIN-1FALCIPARUM-INFECTED ERYTHROCYTESRESISTANT PLASMODIUM-FALCIPARUMHIV-1 ENTRY INHIBITORSHUMAN CEREBRAL MALARIAMEMBRANE ANTIGEN 1IN-VITRO GROWTHSERINE-PROTEASECURDLAN SULFATE\n P. falciparum\n\n P. vivax\nMicrobiology
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