Inhibitory effect of naphthoquine phosphate on Babesia gibsoni in vitro and Babesia rodhaini in vivo

Shengwei Ji,Iqra Zafar,Bumduuren Tuvshintulga,Naoaki Yokoyama,Eloiza May Galon,Xuenan Xuan,Jixu Li,Yae Hasegawa,Aiko Iguchi,Mingming Liu,Mohamed Abdo Rizk

doi:10.1186/s13071-021-05127-0

Abstract

BackgroundDrug resistance and toxic side effects are major challenges in the treatment of babesiosis. As such, new drugs are needed to combat the emergence of drug resistance in Babesia parasites and to develop alternative treatment strategies. A combination of naphthoquine (NQ) and artemisinin is an antimalarial therapy in pharmaceutical markets. The present study repurposed NQ as a drug for the treatment of babesiosis by evaluating the anti-Babesia activity of naphthoquine phosphate (NQP) alone.MethodsAn in vitro growth inhibition assay of NQP was tested on Babesia gibsoni cultures using a SYBR Green I-based fluorescence assay. In addition, the in vivo growth inhibitory effect of NQP was evaluated using BALB/c mice infected with Babesia rodhaini. The parasitemia level and hematocrit values were monitored to determine the therapeutic efficacy of NQP and the clinical improvements in NQP-treated mice.ResultsThe half maximal inhibitory concentration of NQP against B. gibsoni in vitro was 3.3 ± 0.5 μM. Oral administration of NQP for 5 consecutive days at a dose of 40 mg/kg of body weight resulted in significant inhibition of B. rodhaini growth in mice as compared with that of the control group. All NQP-treated mice survived, whereas the mice in the control group died between days 6 and 9 post-infection.ConclusionThis is the first study to evaluate the anti-Babesia activity of NQP in vitro and in vivo. Our findings suggest that NQP is a promising drug for treating Babesia infections, and drug repurposing may provide new treatment strategies for babesiosis.Graphical

Highlights

Drug resistance and toxic side effects are major challenges in the treatment of babesiosis
Because of the close relationship between Plasmodium and Babesia genera, we investigated whether naphthoquine phosphate (NQP) has effects on the in vitro growth of B. gibsoni, a causative agent of canine babesiosis, and in vivo-propagated B. rodhaini, a highly pathogenic rodent Babesia species
The parasitemia in NQP- and TAF-treated groups were decreased after treatment and showed 95.1% (3.8% peak parasitemia) and 95.8% (3.3% peak parasitemia) inhibition compared to the highest parasitemia in the DMSOtreated group, respectively

Summary

Introduction

Drug resistance and toxic side effects are major challenges in the treatment of babesiosis. New drugs are needed to combat the emergence of drug resistance in Babesia parasites and to develop alternative treatment strategies. The present study repurposed NQ as a drug for the treatment of babesiosis by evaluating the anti-Babesia activity of naphthoquine phosphate (NQP) alone. Several Babesia species have been reported to infect humans. Because of the wide range of hosts, babesiosis is one of the most ubiquitous infections of free-living animals and is attracting increasing interest as an emerging zoonosis in humans [1]. Parasites replicate in the mammalian host red blood cells (RBCs) and produce clinical symptoms including fever, hemolytic anemia, anorexia, hemoglobinuria, and emaciation, and the severe infection phase often results in death [2].

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