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.

Bioinformatics Analysis, Cloning and Expression of Spirometra erinaceieuropaei Fatty Acid-Binding Protein

“…Therefore, FABP is considered as a potential and promising anti parasitic vaccine (Dalton et al, 2004). For example, the first identified FABP protein of the parasite, Schistosoma mansoni FABP (Tendler et al, 1996), has been developed as a vaccine, showing good efficacy against Schistosoma mansoni (Qokoyi et al, 2021).…”

Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part III: Helminths

“…Since Elafin is a novel substrate for elastase, i.e. a selective serine protease inhibitor, the reviewer recommended its application on the skin prior to water source contact [38] .…”

“…low similarity (~50%) to their host orthologues, and were functionally characterized since a decade, no further studies were conducted investigating their use as potential drug targets [38] .…”

“…The reviewers recommended combination of selective HSP60 inhibitors with PZQ however; they claimed absence of reports regarding SmHSP60 crystal structure. Therefore, no inhibitors targeting SmHSP60 were developed yet [38] .…”

“…In addition to maintenance of tegument integrity, the TSEs through their interaction together, mediate regulation of signaling pathways for migration of the juvenile flukes. Therefore, TSE inhibitors were proposed promising novel anti-schistosomal drugs [38] .…”