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

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Skidmore, Mark A, Mustaffa, Khairul Mohd Fadzli, Cooper, Lynsay C, Guimond, Scott E, Yates, Edwin A and Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 (2017) 'A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence.'. PLoS ONE, Vol 12, Issue 10, e0186276.

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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
Subjects: QS Anatomy > QS 4 General works. Classify here works on regional anatomy
QW Microbiology and Immunology > QW 52 Physiology and chemistry of microorganisms. Metabolism.
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pone.0186276
Depositing User: Mary Creegan
Date Deposited: 25 Oct 2017 12:03
Last Modified: 17 Jul 2019 14:14
URI: https://archive.lstmed.ac.uk/id/eprint/7749

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