Discovering the in vitro potent inhibitors against Babesia and Theileria parasites by repurposing the Malaria Box: A review

Publication date: Available online 19 July 2019Source: Veterinary ParasitologyAuthor(s): Mohamed Abdo Rizk, Shimaa Abd El-Salam El-Sayed, Sabry El-Khodery, Naoaki Yokoyama, Ikuo IgarashiAbstractThere is an innovative approach to discovering and developing novel potent and safe anti-Babesia and anti-Theileria agents for the control of animal piroplasmosis. Large-scale screening of 400 compounds from a Malaria Box (a treasure trove of 400 diverse compounds with antimalarial activity has been established by Medicines for Malaria Venture) against the in vitro growth of bovine Babesia and equine Babesia and Theileria parasites was performed, and the data were published in a brief with complete dataset from 236 screens of the Malaria Box compounds. Therefore, in this review, we explored and discussed in detail the in vitro inhibitory effects of 400 antimalarial compounds (200 drug-like and 200 probe-like) from the Malaria Box against Babesia (B.) bovis, B. bigemina, B. caballi, and Theileria (T.) equi. Seventeen hits were the most interesting with regard to bovine Babesia parasites, with mean selectivity indices (SIs) greater than 300 and half maximal inhibitory concentration (IC50s) ranging from 50 to 410 nM. The most interesting compounds with regard to equine Babesia and Theileria parasites were MMV020490 and MMV020275, with mean SIs> 258.68 and> 251.55, respectively, and IC50s ranging from 76 to 480 nM. Ten novel anti–B. bovis, anti–B. bigemina, ...
Source: Veterinary Parasitology - Category: Veterinary Research Source Type: research

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Answer to Parasite Case of the Week 554:Babesiaspecies. Without a travel history, the differential diagnosis includesPlasmodium falciparummalaria given that only ring forms are seen and there is a high parasitemia; however, the following features are supportive of babesiosis:1. Multiple (4) small forms within a single cell that are not a clear schizont form ofPlasmodium.2. Easily-identified extracellular forms.3. Lack of malaria pigmentAs Blaine mentioned, the rings are not thin and delicate as would normally be seen withP. falciparuminfection. While thicker rings are commonly seen in'older'blood (i.e., blood that was>2...
Source: Creepy Dreadful Wonderful Parasites - Category: Parasitology Source Type: blogs
In this study, the 400 compounds in the Pathogen Box provided by the Medicines for Malaria Venture foundation were screened against Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi. A fluorescence-based method using SYBR Green 1 stain was used for initial in vitro screening and determination of the half maximal inhibitory concentration (IC50). The initial in vitro screening performed using a 1 μM concentration as baseline revealed nine effective compounds against four tested parasites. Two “hit” compounds, namely MMV021057 and MMV675968, that showed IC50  100 were selected. The IC50s ...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research
Abstract Babesia divergens is an intra-erythrocytic parasite that causes malaria-like symptoms in infected people. As the erythrocyte provides the parasite with the infra-structure to grow and multiply, any perturbation to the cell should impact parasite viability. Support for this comes from the multitude of studies that have shown that the sickle trait has in fact been selected for because of the protection in provides against a related Apicomplexan parasite, Plasmodium that causes malaria. In this paper, we examine the impact of both sickle cell anemia and sickle trait RBC environment on different aspects of th...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Abstract Although Babesia represents an important worldwide veterinary threat and an emerging risk to humans, this parasite has been poorly studied as compared to Plasmodium, its malaria-causing relative. In fact, Babesia employs highly specific survival strategies during its intraerythrocytic development and its intricate journey through the tick vector. This review introduces a substantially extended molecular phylogeny of the order Piroplasmida, challenging previous taxonomic classifications. The intriguing developmental proficiencies of Babesia are highlighted and compared with those of other haemoparasitic Ap...
Source: Trends in Parasitology - Category: Parasitology Authors: Tags: Trends Parasitol Source Type: research
Evaluation of 4-amino 2-anilinoquinazolines against Plasmodium and other apicomplexan parasites in vitro and in a P. falciparum humanized NOD-scid IL2Rγnull mouse model of malaria. Antimicrob Agents Chemother. 2018 Dec 17;: Authors: Gilson PR, Nguyen W, Poole WA, Teixeira JE, Thompson JK, Guo K, Stewart RJ, Ashton TD, White KL, Sanz LM, Gamo FJ, Charman SA, Wittlin S, Duffy J, Tonkin CJ, Tham WH, Crabb BS, Cooke BM, Huston CD, Cowman AF, Sleebs BE Abstract A series of 4-amino 2-anilinoquinazolines optimized for activity against the most lethal malaria parasite of humans, Plasmodium falciparum, w...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Publication date: Available online 7 August 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Marie Jalovecka, David Hartmann, Yukiko Miyamoto, Lars Eckmann, Ondrej Hajdusek, Anthony J. O'Donoghue, Daniel SojkaAbstractBabesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the genus Babesia. Treatment of this emerging malaria-related disease has relied on antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative agent of malaria, has recently been validated as a target for anti-malarial drug development and therefore, in this study, we invest...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research
Abstract Babesia is a tick-borne intraerythrocytic parasite that is clinically and diagnostically similar to malaria parasite, conferring risk of misdiagnosis in areas where both parasites are endemic. Data on Babesia in humans in Africa are lacking, despite evidence that it is present in regional animal populations. Samples that were collected in November 2014 to July 2015 in Kilosa district, Tanzania, were evaluated for evidence of malaria and Babesia infection. Clinical data and laboratory samples (i.e., hemoglobin, rapid diagnostic testing [RDT] for malaria, peripheral blood smear, and dried blood spots) from ...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
In conclusion, seroreactive antigen 5-1-1, a member of the BMN1 protein family, is expressed on the outer surface of B. microti and is a promising candidate antigen for the early diagnosis of babesiosis. rBmSA5-1-1 ELISA and ICT methods show good potential for detecting specific antibodies in mice at different stages of infection. PMID: 29559329 [PubMed - as supplied by publisher]
Source: Acta Tropica - Category: Infectious Diseases Authors: Tags: Acta Trop Source Type: research
Publication date: Available online 8 February 2018 Source:Ticks and Tick-borne Diseases Author(s): Jingwei Huang, Kang Xiong, Houshuang Zhang, Yanzhen Zhao, Jie Cao, Yongzhi Zhou, Haiyan Gong, Jinlin Zhou The intra-erythrocytic apicomplexan Babesia microti is the predominant pathogen that causes human babesiosis, an infectious disease that occurs worldwide. B. microti relies on the antioxidant including thioredoxin system to maintain the redox balance during the erythrocytic stage. In the present study, the full-length B. microti thioredoxin 3 (BmTrx3) gene was cloned, expressed in vitro, and its response to antiprotozoal...
Source: Ticks and Tick borne Diseases - Category: Zoology Source Type: research
Abstract Human red blood cells infected with the malaria parasite Plasmodium falciparum show an increased permeability to a number of solutes. We have previously demonstrated that such infected cells take up glutamate via a member of the excitatory amino acid transporter protein family (EAAT), namely EAAT3. Babesia divergens is a parasite that also infects human erythrocytes, and also induces increased solute permeability, including for glutamate. Here we have investigated whether glutamate uptake in B. divergens infected human red blood cells is also dependent on EAAT3 activity. We find that, although B. divergen...
Source: International Journal of Medical Microbiology - Category: Microbiology Authors: Tags: Int J Med Microbiol Source Type: research
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