Though morbidity and mortality due to malaria have declined in the last 15 years, emerging resistance to first-line artemisinin-based antimalarials, absence of efficacious vaccines and limited chemotherapeutic alternatives imperil the consolidation of these gains. As a blueprint to steer future designs of new medicines, malaria drug discovery recently adopted a descriptive proposal for the ideal candidate molecules and drugs likely to successfully progress into the final stages of clinical development. As an audit of recent developments in the chemotherapy of malaria in the last five years, this review captures a landscape of diverse molecules at various stages of drug development and discusses their progress. In brief, we also discuss how omics data on Plasmodium has been extensively leveraged to identify potential vaccine candidates and putative targets of molecules in development and clinical use as well as map loci implicit in their modes of resistance. Future perspective on malaria drug development should involve a reconciliation of some of the challenges of the target candidate profiles (TCPs), specifically TCP3, with the promise of effective anti-hypnozoite medicines. Similarly, with the recent development of a humanized mouse model that can evaluate the prophylactic potential of candidate drugs, we argue for increased effort at identifying more liver-stage molecules, which are often only secondarily prioritized in conventional screening programs.

中文翻译：

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新型抗疟药物候选物的发现和开发的最新进展

尽管在过去的15年中，由于疟疾引起的发病率和死亡率下降了，但对基于青蒿素的一线抗疟药的耐药性不断增强，缺乏有效的疫苗和有限的化学治疗替代品，阻碍了这些药物的合并。作为指导未来新药设计的蓝图，疟疾药物的发现最近采用了一种描述性建议，用于可能成功进入临床开发最终阶段的理想候选分子和药物。作为对过去五年中疟疾化学疗法最新进展的一次审计，本综述总结了药物开发各个阶段的各种分子的概况，并讨论了它们的进展。简而言之，我们还讨论了疟原虫的组学数据已经广泛地用于鉴定潜在的候选疫苗和在开发和临床应用中分子的推定靶标，以及在其抗药性模式中隐含的作图基因座。未来关于疟疾药物开发的观点应涉及目标候选药物（TCP），特别是TCP3的一些挑战的和解，并有望提供有效的抗次生动物药物。同样，随着可评估候选药物预防潜力的人源化小鼠模型的最新发展，我们主张在鉴定更多肝阶段分子方面付出更多的努力，而在常规筛查程序中，这些分子通常仅次于其他分子。