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

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background: </jats:bold>Drug resistance and severe side effects are major challenges in the treatment of babesiosis as they lead to less choices for treatment. Development of new drugs to enrich the treatment strategies and delay the emergence of drug resistance in parasites is still needed. Naphthoquine (NQ) combined with artemisinin treats <jats:italic>Plasmodium</jats:italic> infection by rapid parasite clearance. The current study repurposed NQ as a babesiosis drug treatment by evaluating the effects of naphthoquine phosphate (NQP) as a single dose treatment for babesiosis. <jats:bold>Methods: </jats:bold><jats:italic>In vitro</jats:italic> anti-<jats:italic>Babesia</jats:italic> activity of <jats:bold></jats:bold>NQP was tested on <jats:italic>Babesia gibsoni </jats:italic>cultures. The inhibition of parasite growth was verified using a SYBR green I-based fluorescence assay. <jats:italic>In vivo</jats:italic> efficacy of NQP was evaluated using BALB/c mice infected with <jats:italic>Babesia rodhaini</jats:italic>. The parasitemia level and hematocrit values were monitored.<jats:bold> </jats:bold><jats:bold>Results: </jats:bold>The half maximal inhibitory concentration of NQP against <jats:italic>B. gibsoni in vitro </jats:italic>was 3.3 ± 0.5 μM. Oral administration of NQP for 5 successive days at a dose of 40 mg/kg of body weight resulted in significant inhibition on parasite growth compared with the control group. All mice in NQP-treated group survived, whereas the mice in control group died between days 6 and 9 post infection.<jats:bold> </jats:bold><jats:bold>Conclusion: </jats:bold>This is the first study to evaluate the anti-<jats:italic>Babesia</jats:italic> activity of NQP <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. The results showed that NQP is a promising drug for babesiosis treatment and drug repurposing may provide new treatment strategies for babesiosis.</jats:p>