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

Langsley, Gordon, Skidmore, Mark A, Mustaffa, Khairul Mohd Fadzli, Cooper, Lynsay C ORCID: 0000-0002-5100-5261, Guimond, Scott E, Yates, Edwin A and Craig, Alister G (2017) A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence. PLOS ONE, 12 (10). ART: e0186276. doi:10.1371/journal.pone.0186276

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Text 14243 Langsley, Skidmore, Mustaffa, Cooper, Guimond, Yates, Craig (2017) A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence.pdf - Published Version Available under License Creative Commons Attribution 4.0. Download (2MB) | Preview

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.

Item Type:	Article
Article Type:	Article
Subjects:	Q Science > QD Chemistry R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Divisions:	Schools and Research Institutes > School of Education and Science
Depositing User:	Anna Kerr
Date Deposited:	22 Jul 2024 09:23
Last Modified:	22 Jul 2024 09:30
URI:	https://eprints.glos.ac.uk/id/eprint/14243

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