埃玛菌素用于控制媒介传播疾病的潜力。

Potential of emodepside for vector-borne disease control.

作者信息

Khemrattrakool Pattarapon, Hongsuwong Thitipong, Phanphoowong Theerawit, Sriwichai Patchara, Poovorawan Kittiyod, Tarning Joel, Kobylinski Kevin C

机构信息

Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Department of Medical Entomology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

出版信息

Malar J. 2025 Jan 11;24(1):9. doi: 10.1186/s12936-025-05250-8.

DOI:10.1186/s12936-025-05250-8

PMID:39815344

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11734516/

Abstract

BACKGROUND

Emodepside is an anthelmintic used in veterinary medicine that is currently under investigation in human clinical trials for the treatment of soil-transmitted helminths and possibly Onchocerca volvulus. Emodepside targets the calcium-activated voltage-gated potassium slowpoke 1 (SLO-1) channels of presynaptic nerves of pharynx and body wall muscle cells of nematodes leading to paralysis, reduced locomotion and egg laying, starvation, and death. Emodepside also has activity against Drosophila melanogaster SLO-1 channels. Orthologous SLO-1 genes are present in Anopheles gambiae and Aedes aegypti, suggesting that emodepside may have activity against mosquitoes.

METHODS

Both Anopheles dirus and Ae. aegypti were blood-fed emodepside across a range of concentrations (1-10,000 nM) and mosquito survival was monitored for 10 days. Co-feeding experiments were also performed with An. dirus blood fed ivermectin at the concentrations that kills 25% (LC) and 50% (LC) of mosquitoes with and without emodepside at clinical peak concentration in humans (C) and five times the C, and mosquito survival was monitored for 10 days.

RESULTS

Emodepside had weak mosquito-lethal effects in An. dirus but none observed in Ae. aegypti at the concentrations evaluated. The An. dirus emodepside LC was 4,623 [4,159-5,066] ng/ml which is > 100-fold greater than the peak concentrations seen in human. The ivermectin and emodepside co-feed experiment with An. dirus did not indicate any altered effect of ivermectin on mosquito survival when emodepside co-fed at human C or five times that of the human C.

CONCLUSIONS

Emodepside was not lethal to An. dirus at human-relevant concentrations and had no effect on Ae. aegypti survival. Thus, mass distribution of emodepside does not appear to be a potential tool for vector-borne disease control. Emodepside induced mortality in An. dirus does suggest that the SLO-1 channel could be a potential target for novel vector control and may warrant further investigation.

摘要

背景

埃莫昔肽是一种用于兽医学的驱虫药，目前正在进行人体临床试验，用于治疗土壤传播的蠕虫以及可能用于治疗盘尾丝虫。埃莫昔肽靶向线虫咽和体壁肌肉细胞突触前神经的钙激活电压门控钾慢poke 1（SLO-1）通道，导致麻痹、运动减少、产卵减少、饥饿和死亡。埃莫昔肽对果蝇的SLO-1通道也有活性。冈比亚按蚊和埃及伊蚊中存在直系同源的SLO-1基因，这表明埃莫昔肽可能对蚊子有活性。

方法

用一系列浓度（1-10,000 nM）的埃莫昔肽对大劣按蚊和埃及伊蚊进行血饲，并监测蚊子存活10天。还用杀死25%（LC）和50%（LC）蚊子的伊维菌素浓度对大劣按蚊进行血饲，在人类临床峰值浓度（C）以及C的五倍浓度下，分别在有和没有埃莫昔肽的情况下进行共饲实验，并监测蚊子存活10天。

结果

在评估的浓度下，埃莫昔肽对大劣按蚊有较弱的杀蚊作用，但在埃及伊蚊中未观察到任何作用。大劣按蚊的埃莫昔肽LC为4,623 [4,159-5,066] ng/ml，这比人类中观察到的峰值浓度高100倍以上。大劣按蚊的伊维菌素和埃莫昔肽共饲实验表明，当以人类C或人类C的五倍浓度共饲埃莫昔肽时，伊维菌素对蚊子存活的影响没有任何改变。