Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Front Cell Infect Microbiol. 2023 Dec 15;13:1308193. doi: 10.3389/fcimb.2023.1308193. eCollection 2023.
Over the last two decades, global malaria cases caused by have declined due to the implementation of effective treatments and the use of insecticides. However, the COVID-19 pandemic caused major disruption in the timely delivery of medical goods and diverted public health resources, impairing malaria control. The emergence of resistance to all existing frontline antimalarials underpins an urgent need for new antimalarials with novel mechanisms of action. Furthermore, the need to reduce malaria transmission and/or prevent malaria infection has shifted the focus of antimalarial research towards the discovery of compounds that act beyond the symptomatic blood stage and also impact other parasite life cycle stages. Phenotypic screening has been responsible for the majority of new antimalarial lead compounds discovered over the past 10 years. This review describes recently reported novel antimalarial hits that target multiple parasite stages and were discovered by phenotypic screening during the COVID-19 pandemic. Their modes of action and targets in blood stage parasites are also discussed.
在过去的二十年中，由于实施了有效的治疗方法和使用杀虫剂，由 引起的全球疟疾病例有所减少。然而，COVID-19 大流行严重扰乱了医疗用品的及时交付，并转移了公共卫生资源，从而影响了疟疾的控制。对所有现有一线抗疟药物的耐药性的出现，迫切需要具有新作用机制的新抗疟药物。此外，需要降低疟疾传播率和/或预防疟疾感染，这使得抗疟研究的重点转向发现作用于症状性血液阶段之外的化合物，也影响其他寄生虫生命周期阶段的化合物。表型筛选在过去 10 年中发现的大多数新的抗疟先导化合物中都起到了至关重要的作用。本文综述了最近报道的新型抗疟药物，这些药物针对多个寄生虫阶段，并通过 COVID-19 大流行期间的表型筛选发现，还讨论了它们在血液阶段寄生虫中的作用模式和靶标。
