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A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence

Skidmore, Mark; Mohd Fadzli Mustaffa, Khairul; Cooper, Lynsay C.; Guimond, Scott E.; Yates, Edwin A.; Craig, Alister G.

A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence Thumbnail


Authors

Khairul Mohd Fadzli Mustaffa

Lynsay C. Cooper

Edwin A. Yates

Alister G. Craig



Abstract

A feature of mature Plasmodium falciparum parasitized red blood cells is their ability to bind surface molecules of the microvascular endothelium via the parasite-derived surface protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). This ligand is associated with the cytoadherence pathology observed in severe malaria. As pRBC treated with effective anti-malarial drugs are still able to cytoadhere, there is therefore a need to find an adjunct treatment that can inhibit and reverse the adhesion process. One semi-synthetic, sulfated polysaccharide has been identified that is capable of inhibiting and reversing sequestration of pRBC on endothelial cells in vitro under physiological flow conditions. Furthermore, it exhibits low toxicity in the intrinsic (APTT assay) and extrinsic (PT assay) clotting pathways, as well as exhibiting minimal effects on cell (HUVEC) viability (MTT proliferation assay). These findings suggest that carbohydrate-based anti-adhesive candidates may provide potential leads for therapeutics for severe malaria.

Journal Article Type Article
Acceptance Date Sep 28, 2017
Publication Date Oct 18, 2017
Publicly Available Date Mar 28, 2024
Journal PLoS One
Print ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 12
Issue 10
Article Number e0186276
DOI https://doi.org/10.1371/journal.pone.0186276
Keywords Antimalarials, Cell Adhesion, Cell Proliferation, Endothelial Cells, Erythrocytes, Glycosaminoglycans, Human Umbilical Vein Endothelial Cells, Humans, Malaria, Falciparum, Plasmodium falciparum, Protozoan Proteins
Publisher URL https://doi.org/10.1371/journal.pone.0186276

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