A new heparan sulfate from the mollusk Nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of Plasmodium falciparum

Abstract

BACKGROUND Despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of Plasmodium falciparum -infected erythrocytes (Pf-iEs). OBJECTIVES In this context, we evaluated a new heparan sulfate (HS) from Nodipecten nodosus for antimalarial activity and inhibition of P. falciparum cytoadhesion and rosetting. METHODS Parasite inhibition was measured by SYBR green using a cytometer. HS was assessed in rosetting and cytoadhesion assays under static and flow conditions using Chinese hamster ovary (CHO) and human lymphatic endothelial cell (HLEC) cells expressing intercellular adhesion molecule-1 (ICAM1) and chondroitin sulfate A (CSA), respectively. FINDINGS This HS inhibited merozoite invasion similar to heparin. Moreover, mollusk HS decreased cytoadherence of P. falciparum to CSA and ICAM-1 on the surface of endothelial cells under static and flow conditions. In addition, this glycan efficiently disrupted rosettes. CONCLUSIONS These findings support a potential use for mollusk HS as adjunct therapy for severe malaria.

Unveiling the Sugary Secrets of Plasmodium Parasites

“…Naturally derived HLMs from marine organisms were examined for their antimalarial efficacy. Heparan sulfate isolated from lion's paw scallops and fucosylated chondroitin sulfate isolated from sea cucumbers efficiently inhibit merozoite invasion and cytoadherence in vitro (Bastos et al, 2014(Bastos et al, , 2019. Both GAGs can be readily obtained from natural sources and showed less anticoagulating activity than heparin.…”

Antiparasitic Effects of Sulfated Polysaccharides from Marine Hydrobionts

“…The later work of M.F. Bastos et al [65] presented materials on the study of antimalarial effect and the ability to inhibit cytoadhesion of heparan sulfate from the scallop Nodipecten nodosus. The polysaccharide is formed by repeating the disaccharide units of β-D-glucuronic acid 1 → 4 N-acetyl-α-D-glucosamine containing rare sulfate groups at the C2 or C3 positions of glucuronic acid.…”

Enhanced Antimalarial Efficacy Obtained by Targeted Delivery of Artemisinin in Heparin-Coated Magnetic Hollow Mesoporous Nanoparticles

“…The invasion of both hepatocytes and RBCs by P. falciparum requires engagement of parasite-derived ligands and host cell receptors, which are predominantly glycosaminoglycans, such as sialic acids, , heparan sulfate, , or heparinlike carbohydrates. , Heparin has demonstrated an excellent invasion inhibitory effect on P. falciparum in vitro and antidisease efficacy in malarial patients in various formats. − Blocking iRBC adhesion to the endothelial surface as well as inhibiting merozoite attachment to the RBC surface have been the main mechanisms. ,, Heparin-derived molecules without an anticoagulant activity have been proposed as promising antimalarial drugs. ,, Recently, heparin surface-functionalized nanoparticles have been successfully developed as a promising platform for targeted antimalarial drug delivery. , In another representative example, a mimetic structure of the RBC membrane with a heparin coating was presented as a nanotechnological strategy for blocking invasion of merozoite to RBCs …”

“…17,18 However, constructing a well-functioning nanodrug-delivery system against malaria is challenging, which needs to be perfectly integrated with the developmental characteristics of the malarial parasite to maximize its antimalarial effect. The invasion of both hepatocytes and RBCs by P. falciparum requires engagement of parasite-derived ligands and host cell receptors, which are predominantly glycosaminoglycans, such as sialic acids, 19,20 heparan sulfate, 21,22 or heparinlike carbohydrates. 23,24 Heparin has demonstrated an excellent invasion inhibitory effect on P. falciparum in vitro and antidisease efficacy in malarial patients in various formats.…”