Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future

Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. Presented here is an overview of the evolution over the last three to four decades of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa. Target selection is a crucial and multi-faceted aspect of structure-guided drug design. The major impact of advances in molecular biology, genome sequencing and high-throughput screening is touched upon. The most advanced crystallographic techniques, including XFEL, have already been applied to structure determinations of drug targets from parasitic protozoa. Even cryo-electron microscopy is contributing to our understanding of the mode of binding of inhibitors to parasite ribosomes. A number of projects have been selected to illustrate how structural information has assisted in arriving at promising compounds that are currently being evaluated by pharmacological, pharmacodynamic and safety tests to assess their suitability as pharmaceutical agents. Structure-guided approaches are also applied to incorporate properties into compounds such that they are less likely to become the victim of resistance mechanisms. A great increase in the number of novel antiparasitic compounds will be needed in the future. These should then be combined into various multi-compound therapeutics to circumvent the diverse re...
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Tags: parasitic protozoa antiparasitic drug discovery research communications Source Type: research

Related Links:

Publication date: Available online 3 April 2020Source: Parasitology InternationalAuthor(s): Hirotaka Katahira, Hana Ashida, Mari Kobayashi
Source: Parasitology International - Category: Parasitology Source Type: research
imarães S Abstract Giardia duodenalis is one of the most important and widespread gastrointestinal parasites in the world. Despite its relevance as a causative agent of diarrhea, asymptomatic giardiasis occurs frequently, especially in low resources settings in which children are exposed to many risk factors. Based on microscopic examination and the polymerase chain reaction (PCR) amplification and sequencing of beta-giardin (bg), triose phosphate isomerase (tpi) and glutamate dehydrogenase (gdh) genes, we assessed G. duodenalis occurrence and genetic diversity in isolates of children attending a daycare ce...
Source: Revista do Instituto de Medicina Tropical de Sao Paulo - Category: Tropical Medicine Authors: Tags: Rev Inst Med Trop Sao Paulo Source Type: research
Abstract SUMMARYWhile flagella have been studied extensively as motility organelles, with a focus on internal structures such as the axoneme, more recent research has illuminated the roles of the flagellar surface in a variety of biological processes. Parasitic protists of the order Kinetoplastida, which include trypanosomes and Leishmania species, provide a paradigm for probing the role of flagella in host-microbe interactions and illustrate that this interface between the flagellar surface and the host is of paramount importance. An increasing body of knowledge indicates that the flagellar membrane serves a mult...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Microbiol Mol Biol Rev Source Type: research
Publication date: Available online 3 April 2020Source: International Journal for Parasitology: Parasites and WildlifeAuthor(s): Anna M. Pyziel, Aleksander W. Demiaszkiewicz, Barbara Osińska, Izabella Dolka, Krzysztof Anusz, Zdzisław Laskowski
Source: International Journal for Parasitology: Parasites and Wildlife - Category: Parasitology Source Type: research
(Monash University) Australian Scientists have shown that an anti-parasitic drug already available around the world can kill the virus -- effectively eradicating all genetic material of the virus within 48 hours. Scientists from Monash University in Melbourne showed that a single dose of the drug, Ivermectin, could stop the SARS-CoV-2 virus growing in cell culture -
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Eimeria necatrix, the most highly pathogenic coccidian in chicken small intestines, can cause high morbidity and mortality in susceptible birds and devastating economic losses in poultry production, but the under...
Source: Parasites and Vectors - Category: Microbiology Authors: Tags: Research Source Type: research
Babesia spp. are apicomplexan parasites which infect a wide range of mammalian hosts. Historically, most Babesia species were described based on the assumed host specificity and morphological features of the intr...
Source: Parasites and Vectors - Category: Microbiology Authors: Tags: Research Source Type: research
Rhipicephalus microplus, an invasive tick species of Asian origin and the main vector of Babesia species, is considered one of the most widespread ectoparasites of livestock. The tick has spread from its native h...
Source: Parasites and Vectors - Category: Microbiology Authors: Tags: Research Source Type: research
Smad proteins are essential cellular mediators within the transforming growth factor- β (TGF-β) superfamily. They directly transmit incoming signals from the cell surface receptors to the nucleus. In spite of t...
Source: Parasites and Vectors - Category: Microbiology Authors: Tags: Research Source Type: research
Triatomine bugs are responsible for the vectorial transmission of the parasite Trypanosoma cruzi, etiological agent of Chagas disease, a zoonosis affecting 10 million people and with 25 million at risk of infecti...
Source: Parasites and Vectors - Category: Microbiology Authors: Tags: Research Source Type: research
More News: Biochemistry | Biology | Chemistry | Education | Molecular Biology | Parasitic Diseases | Parasitology | Universities & Medical Training