Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi

Marta G Silva,Rozalia A Dodean,Michael K Riscoe,Carlos E Suarez,J Stone Doggett,Rolf Winter,Aaron Nilsen,Sovitj Pou,Reginaldo G Bastos

doi:10.1186/s13071-020-04487-3

Abstract

BackgroundThe most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. Treatment and control of these diseases are usually achieved using potentially toxic chemotherapeutics, such as imidocarb diproprionate, but drug-resistant parasites are emerging, and alternative effective and safer drugs are needed. The endochin-like quinolones (ELQ)-300 and ELQ-316 have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp., with ELQ-316 also being effective against Babesia microti, without showing toxicity in mammals.MethodsThe inhibitory effects of ELQ-300 and ELQ-316 were assessed on the growth of cultured B. bovis, B. bigemina, B. caballi and T. equi. The percentage of parasitized erythrocytes was measured by flow cytometry, and the effect of the ELQ compounds on the viability of horse and bovine peripheral blood mononuclear cells (PBMC) was assessed by monitoring cell metabolic activity using a colorimetric assay.ResultsWe calculated the half maximal inhibitory concentration (IC50) at 72 h, which ranged from 0.04 to 0.37 nM for ELQ-300, and from 0.002 to 0.1 nM for ELQ-316 among all cultured parasites tested at 72 h. None of the parasites tested were able to replicate in cultures in the presence of ELQ-300 and ELQ-316 at the maximal inhibitory concentration (IC100), which ranged from 1.3 to 5.7 nM for ELQ-300 and from 1.0 to 6.0 nM for ELQ-316 at 72 h. Neither ELQ-300 nor ELQ-316 altered the viability of equine and bovine PBMC at their IC100 in in vitro testing.ConclusionsThe compounds ELQ-300 and ELQ-316 showed significant inhibitory activity on the main parasites responsible for bovine babesiosis and equine piroplasmosis at doses that are tolerable to host cells. These ELQ drugs may be viable candidates for developing alternative protocols for the treatment of bovine babesiosis and equine piroplasmosis.Graphical

Highlights

The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis
endochin-like quinolones (ELQ)‐300 and ELQ‐316 inhibit the growth of B. bovis, B. bigemina, B. caballi and T. equi The effect of ELQ-300 and ELQ-316 on parasite growth, with a starting percentage of parasitized erythrocytes (PPE) of 0.2%, was evaluated using seven different concentrations of each compound, ranging from 0.05 to 50 nM
In addition to the acceptable IC50 inhibitory values found for ELQ-300, our study showed even lower ELQ-316 IC50 values for B. bovis, B. bigemina, B. caballi and T. equi, suggesting that these parasites are highly susceptible to these two drugs

Summary

Introduction

The most common apicomplexan parasites causing bovine babesiosis are Babesia bovis and B. bigemina, while B. caballi and Theileria equi are responsible for equine piroplasmosis. No vaccines are currently available against T. equi and B. caballi, and considerable resources have been spent to develop drugs to treat animals against the harmful effects of acute EP and to prevent the loss of performance in chronically infected, high-value horses. Despite these efforts, horses that survive acute infection, especially when caused by T. equi, become persistently infected, asymptomatic carriers, a condition that can be associated with the resurgence of outbreaks of EP worldwide [8]

Methods

Results

Conclusion