Proteins as Targets in Anti-Schistosomal Drug Discovery and Vaccine Development

Abstract

Proteins hardly function in isolation; they form complexes with other proteins or molecules to mediate cell signaling and control cellular processes in various organisms. Protein interactions control mechanisms that lead to normal and/or disease states. The use of competitive small molecule inhibitors to disrupt disease-relevant protein–protein interactions (PPIs) holds great promise for the development of new drugs. Schistosome invasion of the human host involves a variety of cross-species protein interactions. The pathogen expresses specific proteins that not only facilitate the breach of physical and biochemical barriers present in skin, but also evade the immune system and digestion of human hemoglobin, allowing for survival in the host for years. However, only a small number of specific protein interactions between the host and parasite have been functionally characterized; thus, in-depth understanding of the molecular mechanisms of these interactions is a key component in the development of new treatment methods. Efforts are now focused on developing a schistosomiasis vaccine, as a proposed better strategy used either alone or in combination with Praziquantel to control and eliminate this disease. This review will highlight protein interactions in schistosomes that can be targeted by specific PPI inhibitors for the design of an alternative treatment to Praziquantel.

Keywords

• protein–protein interactions
• schistosomiasis
• praziquantel
• S<i>m</i>-Tsp-2/Alhydrogel
• S<i>m</i>-P80/Gla-Se
• S<i>m</i>14/Gla-Se