针对受感染的宿主细胞血液代谢,杀死疟疾寄生虫
Faiza A Siddiqui1, Swamy R Adapa2,3, Xiaolian Li1
1Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Pharmaceuticals (Basel, Switzerland)
|January 28, 2026
概括
一种新的"诱和杀死"疟疾治疗策略使用5-氨基氨酸 (ALA) 来使受感染的红细胞 (RBC) 对二甲素 (DHA) 敏感,克服甲素耐药性.
科学领域:
- 生物化学 生物化学
- 寄生虫学的寄生虫学
- 药物发现 药物发现 药物发现
背景情况:
- 疟疾对全球健康构成重大挑战,而素耐药性则加剧了这一问题.
- 甲素的有效性与和氨酸的化学反应有关.
- 利用宿主红细胞 (RBC) 血代谢提供了潜在的治疗脆弱性.
研究的目的:
- 开发和评估主机指导的"诱和杀死"策略.
- 选择性地使疟疾感染的红血细胞对艺术素敏感.
主要方法:
- 对红细胞和感染Plasmodium falciparum的红细胞 (iRBC) 的定量蛋白质组学和转录组学分析.
- 在体外疟疾培养试验中,使用5 - 氨基氨酸 (ALA) 和二甲胺素 (DHA).
- 评估药物协同作用,氨酸积累,活性氧物种 (ROS) 诱导和寄生虫存活率,包括抗素的分离物.
主要成果:
- 没有感染的红细胞对ALA无透,而iRBC选择性地积累.
- 结合ALA和DHA证明了协同作用的寄生虫消除.
- 实现了对美西宁耐药P.falciparum的完全清除,没有复发.
结论:
- 这种"诱和杀死"策略有效地准宿主RBC的血代谢,以恢复素的疗效.
- 这种以宿主为导向的方法绕过了疟疾寄生虫的抵抗机制.
- 该战略利用临床上安全的化合物用于潜在的疟疾治疗和组合疗法开发.
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