Qokoyi Ndibonani Kebonang, Masamba Priscilla, Kappo Abidemi Paul
Molecular Biophysics and Structural Biology (MBSB) Group, Department of Biochemistry, Kingsway Campus, University of Johannesburg, Auckland Park 2006, South Africa.
Vaccines (Basel). 2021 Jul 8;9(7):762. doi: 10.3390/vaccines9070762.
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.
蛋白质很少单独发挥作用;它们与其他蛋白质或分子形成复合物,以介导细胞信号传导并控制各种生物体中的细胞过程。蛋白质相互作用控制着导致正常和/或疾病状态的机制。使用竞争性小分子抑制剂破坏与疾病相关的蛋白质-蛋白质相互作用(PPI),对新药开发具有巨大潜力。血吸虫对人类宿主的侵袭涉及多种跨物种蛋白质相互作用。病原体表达特定蛋白质,这些蛋白质不仅有助于突破皮肤中存在的物理和生化屏障,还能逃避免疫系统并消化人类血红蛋白,从而使其在宿主体内存活数年。然而,宿主与寄生虫之间只有少数特定的蛋白质相互作用在功能上得到了表征;因此,深入了解这些相互作用的分子机制是开发新治疗方法的关键组成部分。目前的努力集中在开发血吸虫病疫苗上,这是一种提议的更好策略,可单独使用或与吡喹酮联合使用来控制和消除这种疾病。本综述将重点介绍血吸虫中的蛋白质相互作用,这些相互作用可被特定的PPI抑制剂靶向,用于设计替代吡喹酮的治疗方法。