Efficacy and mechanism of actions of cipargamin as an antibabesial drug candidate

Author:

Li Hang,Ji Shengwei,Ariefta Nanang R.,Galon Eloiza May S.,El-Sayed Shimaa AES,Jia Lijun,Nishikawa Yoshifumi,Liu MingmingORCID,Xuan Xuenan

Abstract

AbstractBabesiosis is a disease brought on by intraerythrocytic parasites of the genusBabesia. Current chemotherapies are accompanied by side effects and parasite relapse. Therefore, it is crucial to develop highly effective drugs againstBabesia. Cipargamin (CIP) has shown inhibition against apicomplexan parasites, mainlyPlasmodiumandToxoplasma. This study evaluated the growth-inhibiting properties of CIP againstBabesiaspp. and investigated the mechanism of CIP onB. gibsoni. The half inhibitory concentration (IC50)values of CIP against thein vitrogrowth ofB. bovisandB. gibsoniwere 20.2 ± 1.4 nM and 69.4 ± 2.2 nM, respectively. CIP significantly inhibited the growth ofB. microtiandB. rodhaini in vivo.Resistance was conferred by L921V and L921I mutations inBgATP4, which reduced the sensitivity to CIP by 6.1-and 12.8-fold. Anin silicoinvestigation revealed reductions in affinity for CIP binding toBgATP4L921VandBgATP4L921Icompared toBgATP4WT. In this study, we characterized the efficacy of CIP againstBabesiaspp. by investigating the mechanistic basis for the resistance to CIP conferred by mutations in theBgATP4. Our findings present a promising starting point for the establishment of new therapeutic interventions againstBabesiainfection.

Publisher

Cold Spring Harbor Laboratory

Reference40 articles.

1. Babesiosis and Theileriosis in North America

2. Sparsomycin Exhibits Potent Antiplasmodial Activity In Vitro and In Vivo

3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT04675931, To evaluate efficacy, safety, tolerability and PK of intravenous cipargamin in participants with severe Plasmodium falciparum malaria; 2024 Feb 29 [cited 2024 Apr 9]. Available from: https://clinicaltrials.gov/study/NCT04675931

4. Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum

5. Cell Swelling Induced by the Antimalarial KAE609 (Cipargamin) and Other PfATP4-Associated Antimalarials

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3