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.
Highlights
Protein–protein interactions (PPIs) have gained interest as potential drug targets for a broad range of diseases, such as tropical infections, cancer and neurological disorders, among others
The most clinically important species are Schistosoma mansoni, which is the most common species in Africa, transmitted by Biomphalaria snails, that causes intestinal and hepatic disease; S. japonicum, transmitted by Oncomelania snails, which results in intestinal schistosomiasis in China, Indonesia and the Philippines [8]; and S. haematobium, another common African species that is transmitted by Bulinus snails and causes urogenital schistosomiasis [9]
No drug has been designed by targeting protein–protein interactions (PPIs) in schistosomiasis, a few protein interactions have shown potential as therapeutic targets against schistosomiasis, such as Schistosoma mansoni 29 kilodalton protein (Sm29) and Sm14
Summary
Protein–protein interactions (PPIs) have gained interest as potential drug targets for a broad range of diseases, such as tropical infections, cancer and neurological disorders, among others. Schistosomes have complex life cycles involving two hosts: an intermediate snail host and the definitive human host Their development begins when eggs are released from an infected individual, either through urine or feces, and find their way to fresh water where they hatch and develop into free-swimming miracidia. The miracidium seeks and locates its intermediate host, the snail, where it reproduces and gives rise to multicellular sporocytes These develop into cercariae (larvae), consisting of two embryonic suckers and a two-branched tail, which are capable of infecting humans [10]. For over 20 years, PZQ has become the most effective, common and widely used drug for the treatment of schistosomiasis due to its cost effectiveness, availability and minimal side effects on the patient It is a pyrazine-isoquinoline derivative, first discovered in 1972, and was primarily developed for veterinary use against cestode infection [11]. The alpha-1 glycoprotein is located in the subshell area of mature eggs, where it regulates IL-4-mediated Th2 responses, and is reported to induce a potent anti-inflammatory response by inducing regulatory B cells to produce IL-10 [25]
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