Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds

Abstract

In the present study, we screened 502 natural product compounds against the in vitro growth of Babesia (B.) bovis. Then, the novel and potent identified compounds were further evaluated for their in vitro efficacies using viability and cytotoxicity assays. The in vivo inhibitory effects of the selected compounds were evaluated using B. microti “rodent strain” in mice model. Three potent compounds, namely, Rottlerin (RL), Narasin (NR), Lasalocid acid (LA), exhibited the lowest IC50 (half-maximal inhibitory concentration) as follows: 5.45 ± 1.20 μM for RL, 1.86 ± 0.66 μM for NR, and 3.56 ± 1.41 μM for LA. The viability result revealed the ability of RL and LA to prevent the regrowth of treated parasite at 4 × IC50 and 2 × IC50, respectively, while 4 × IC50 of NR was sufficient to stop the regrowth of parasite. The hematology parameters of B. microti in vivo were different in the NR-treated groups as compared to the infected/untreated group. Interestingly, intraperitoneal administration of NR exhibiting inhibition in the growth of B. microti in mice was similar to that observed after administration of the commonly used antibabesial drug, diminazene aceturate (DA) (76.57% for DA, 74.73% for NR). Our findings indicate the richness of natural product compounds by novel potent antibabesial candidates, and the identified potent compounds, especially NR, might be used for the treatment of animal babesiosis.

Repurposed Drugs That Activate Autophagy in Filarial Worms Act as Effective Macrofilaricides

“…We, therefore, also explored the potency of Rottlerin in vivo and its potential use as a repurposed candidate for this proof-of-concept study. As the compound was shown to be effective in other systems when administered orally [ 37 , 38 ], we treated infected gerbils with Rottlerin 50 mg/kg PO, BID, for 10 days. Although the treatment had no effect on worm burden, there was a significant decrease in Wolbachia loads ( Figure 8 A) in the worms recovered from treated gerbils, as we observed in vitro ( Table S2 ).…”

Antiparasitic Evaluation of Aquiluscidin, a Cathelicidin Obtained from Crotalus aquilus, and the Vcn-23 Derivative Peptide against Babesia bovis, B. bigemina and B. ovata

“…[ 9 , 18 , 19 , 20 , 23 ]. This situation has motivated the research and development of new babesiacidal components and various compounds have been evaluated for this purpose [ 39 ]. Antimicrobial peptides (AMP’s) have been identified from different sources, most of them come from animal species [ 22 ].…”

Comparative efficacy of buparvaquone and imidocarb in inhibiting the in vitro growth of Babesia bovis

“…In addition, vaccination of less than year-old calves using live attenuated parasites, one of the main strategies for babesiosis control and prevention, needs to be integrated strategically to maintain enzootic stability in endemic areas ( Smith et al, 2000 ; Asrar et al, 2022 ). Chemotherapy against bovine babesiosis is an important component in the control of the disease and several drugs and drug combinations have been reported to be effective against the parasite ( Kuttler and Aliu, 1984 ; Silva et al, 2018 ; Silva et al, 2020 ; Li et al, 2021 ; Rizk et al, 2023 ). Treatment success is dependent on early diagnosis, the severity of the disease, the dosage used, the timing of treatment in the course of infection, and the length of time that the drug is present to affect the parasite ( Mehlhorn, 2016 ).…”