Malaria Parasite Plasmodium falciparum Proteins on the Surface of Infected Erythrocytes as Targets for Novel Drug Discovery

Abstract

Specific adhesion (sequestration) of Plasmodium falciparum parasite-infected erythrocytes (IEs) in deep vascular beds can cause severe complications resulting in death. This review describes our work on the discovery, characterization, and optimization of novel inhibitors that specifically prevent adhesion of IEs to the host vasculature during severe malaria, especially its placental and cerebral forms. The main idea of using anti-adhesion drugs in severe malaria is to release sequestered parasites (or prevent additional sequestration) as quickly as possible. This may significantly improve the outcomes for patients with severe malaria by decreasing local and systemic inflammation associated with the disease and reestablishing the microvascular blood flow. To identify anti-malarial adhesion-inhibiting molecules, we have developed a high-throughput (HT) screening approach and found a number of promising leads that can be further developed into anti-adhesion drugs providing an efficient adjunct therapy against severe forms of malaria.

Keywords: PfEMP1 proteins; Plasmodium falciparum; anti-adhesion compounds; cytoadhesion; high-throughput screening; severe malaria.

Role of IE cytoadhesion mediated by the interactions of PfEMP1 proteins with host receptors in the pathology of malaria and its implications for anti-adhesion therapy