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Entamoeba histolytica is the conductive agent of amoebiasis. Upon the parasite's infection, macrophages and neutrophils are activated by interferon γ, IL-13 and tumour necrosis factor. These immune cells then carry out the amoebicidal activity by releasing nitric oxide synthase and reactive oxygen species (ROS). This review talks about the protective and destructive role of ROS in Eh. E. histolytica has defence strategies against oxidative stress which is a result of excess ROS production. They possess antioxidants for their defence such as L-Cysteine, flavodiiron proteins, peroxiredoxin and trichostatin A, which contribute to the parasite's virulence. The ROS are harmful to the host cells as excess ROS production stimulates cell death by mechanisms like apoptosis and necroptosis. NADPH oxidase (NOX) is a key source of ROS in mammalian cells and causes apoptosis of host cells via the protein kinase transduction pathway. This review provides insights into why NOX inhibitors that could be a potent antiparasitic drug, is not effective for in vivo purposes. This paper also gives an insight into a solution that could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development.

Entamoeba histolytica (Eh), a parasitic protozoan and the causative agent of invasive Amoebiasis, invade the host tissue through an effective secretory pathway. There are several lines of evidence suggesting that amoebic trophozoite pore‐forming complex amoebapore and a large class of proteases enzymes including rhomboid proteases, cysteine proteases, and metalloproteases are implicated in host tissue invasion. For successful delivery of these molecules/cargos, trophozoites heavily rely on sorting machinery from the endoplasmic reticulum, Golgi to plasma membrane. Although, sole secretion machinery in E. histolytica is not characterized yet. Therefore, here our aim is to understand the properties of key molecules N‐ethylmaleimide‐sensitive fusion protein attached to protein receptors (SNAREs) in E. histolytica. SNAREs proteins are an important component of the membrane‐trafficking machinery and have been associated in a range of processes including vesicle tethering, fusion as well as specificity of vesicular transport in all eukaryotic cells. SNARE proteins are architecturally simple, categorized by the presence of one copy of a homologous coiled‐coil forming motif. However, the structural information and protein‐protein interaction study of Eh‐associated syntaxin proteins are still not known. Here, we characterize the syntaxin 1 like molecule and VAMP from Eh through physiochemical profiling, modeling, atomistic simulation, protein‐protein interaction, and docking approaches on the proteins containing SNARE and synaptobrevin domain. The modeled structures and the critical residues recognized through protein interaction and docking study may provide better structural and functional insights into these proteins and may aid in the development of newer diagnostic assays.

This chapter focuses on the solutions to emerging multidrug resistance in the major parasitic protozoa plaguing the world. These neglected pathogens have seized the developing nations in a vice-like grip and are seeping into the industrialised world with the dramatic increase in global travel. The alarming rise in resistance to most antiparasitic drugs has left even the wealthiest nations vulnerable. Multidrug resistance occurs to give a survival advantage to the parasite; it has been hastened by the uncontrolled use of chemotherapeutics. This chapter categorises the recent developments to overcome the MDR hurdle under different approaches. The synthesis of novel organic compounds and high-throughput screenings of new chemical entities are two major approaches. Protease and topoisomerase inhibitors of parasitic protozoa prove as worthy drug targets. In-silico and proteomics-based methods also accelerate drug discovery by creating potential drug libraries specific to tropical protozoa. A cost effective and rapid method of combating drug resistance is the repurposing of licensed medicines. This approach also accounts for the established safety of drugs and high commercial availability. Molecular advancements have introduced small interfering RNAs (siRNAs) at preclinical levels as therapeutics functioning via a unique mechanism. The nanoparticle and cell-penetrating peptides (CPP) based delivery of siRNAs has facilitated a stable and low toxic way to silence genes providing pathogenicity and resistance. This will help in reversing MDR and breathing new life into the existing licensed antiprotozoal chemotherapies.