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应对耐药性:消除疟疾时代的新型抗疟药物与新的寄生虫靶点

Tackling resistance: emerging antimalarials and new parasite targets in the era of elimination.

作者信息

Mathews Emily S, Odom John Audrey R

机构信息

Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.

出版信息

F1000Res. 2018 Aug 1;7. doi: 10.12688/f1000research.14874.1. eCollection 2018.

Abstract

Malaria remains a significant contributor to global human mortality, and roughly half the world's population is at risk for infection with spp. parasites. Aggressive control measures have reduced the global prevalence of malaria significantly over the past decade. However, resistance to available antimalarials continues to spread, including resistance to the widely used artemisinin-based combination therapies. Novel antimalarial compounds and therapeutic targets are greatly needed. This review will briefly discuss several promising current antimalarial development projects, including artefenomel, ferroquine, cipargamin, SJ733, KAF156, MMV048, and tafenoquine. In addition, we describe recent large-scale genetic and resistance screens that have been instrumental in target discovery. Finally, we highlight new antimalarial targets, which include essential transporters and proteases. These emerging antimalarial compounds and therapeutic targets have the potential to overcome multi-drug resistance in ongoing efforts toward malaria elimination.

摘要

疟疾仍然是导致全球人类死亡的一个重要因素,全球约一半人口面临感染疟原虫的风险。在过去十年中,积极的控制措施已显著降低了全球疟疾的流行率。然而,对现有抗疟药物的耐药性仍在继续蔓延,包括对广泛使用的青蒿素联合疗法的耐药性。因此,迫切需要新型抗疟化合物和治疗靶点。本综述将简要讨论目前几个有前景的抗疟药物研发项目,包括artefenomel、ferroquine、cipargamin、SJ733、KAF156、MMV048和tafenoquine。此外,我们还将介绍近期在靶点发现中发挥重要作用的大规模基因和耐药性筛选。最后,我们将重点介绍新的抗疟靶点,包括必需转运蛋白和蛋白酶。这些新兴的抗疟化合物和治疗靶点有可能在当前消除疟疾的努力中克服多药耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa2e/6073090/5c6be413c0e5/f1000research-7-16190-g0000.jpg

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