Title:Therapeutic Approaches Blocking Glycan Synthesis as Targeting Strategy for Malaria
Volume: 12
Issue: 1
Author(s): Pollyanna S. Gomes and Alexandre Morrot*
Affiliation:
- Instituto de Microbiologia, Universidade Federal do Rio de Janeiro (UFRJ), CCS - Sala D1-035, Av. Carlos Chagas Filho, 373 - Cidade Universitária, CEP 21.941-902, Ilha do Fundão, Rio de Janeiro, RJ,Brazil
Keywords:
Malaria, pathogenesis, parasite-host interactions, glycobiology, drug-resistance, carbohydrates target, antimalarials.
Abstract: Over one million people die from malaria each year, mainly in the world’s tropical and
sub-tropical areas. Several research efforts have been devoted to the design of new therapeutic targets
for disease control, as drug resistance is one of the greatest challenges in malaria eradication.
Carbohydrate recognition in Plasmodium-host interactions is one area for potential targets against
disease. The glycan derivatives interfere with replication and invasion of Plasmodium falciparum.
Sulfated glycosaminoglycans (GAGs) are known to block merozoite and sporozoite invasion. Heparin
is a GAG that has been shown blocking the invasion by binding to the specific domain of merozoites
surface (MSP) termed MSP-1. Although MSP does not bind to heparin-like GAG oligosaccharides,
its ability to bind to small molecules has not yet been investigated. Besides this, the red blood cell
also has glycans on the surface that mediate parasites-cell and cell-cell interactions. In this review,
we aim to discuss drug mechanisms that act in carbohydrate synthesis targets in malaria disease.