Leishmaniasis is a group of neglected tropical diseases caused by at least 20 species of Leishmania protozoa, which are spread by the bite of infected sandflies. There are three main forms of the disease: cutaneous leishmaniasis (CL, the most common), visceral leishmaniasis (VL, also known as kala-azar, the most serious), and mucocutaneous leishmaniasis. One billion people live in areas endemic to leishmaniasis, with an annual estimation of 30,000 new cases of VL and more than 1 million of CL. New treatments for leishmaniasis are an urgent need, as the existing ones are inefficient, toxic, and/or expensive. We have revised the experimental structure-based drug design (SBDD) efforts applied to the discovery of new drugs against leishmaniasis. We have grouped the explored targets according to the metabolic pathways they belong to, and the key achieved advances are highlighted and evaluated. In most cases, SBDD studies follow high-throughput screening campaigns and are secondary to pharmacokinetic optimization, due to the majoritarian belief that there are few validated targets for SBDD in leishmaniasis. However, some SBDD strategies have significantly contributed to new drug candidates against leishmaniasis and a bigger number holds promise for future development.

中文翻译：

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基于实验结构的药物设计 (SBDD) 抗利什曼病药物应用：范式转变？

利什曼病是一组被忽视的热带疾病，由至少 20 种利什曼原虫引起，通过受感染的白蛉叮咬传播。该病主要分为三种形式：皮肤利什曼病（CL，最常见）、内脏利什曼病（VL，也称为黑热病，最严重）和粘膜皮肤利什曼病。 10 亿人生活在利什曼病流行地区，每年估计新增 VL 病例 30,000 例，CL 病例超过 100 万例。迫切需要治疗利什曼病的新疗法，因为现有疗法效率低下、有毒和/或昂贵。我们修改了用于发现抗利什曼病新药的基于实验结构的药物设计（SBDD）工作。我们根据探索的目标所属的代谢途径对它们进行了分组，并强调和评估了所取得的关键进展。在大多数情况下，SBDD 研究遵循高通量筛选活动，并且次要于药代动力学优化，因为大多数人认为 SBDD 在利什曼病中几乎没有经过验证的靶标。然而，一些 SBDD 策略对抗利什曼病的新候选药物做出了重大贡献，并且更多的策略有望用于未来的开发。