Abstract：
Leishmaniasis, a complex disease caused by at least 20 species of unicellular parasites of the genus Leishmania, disproportionately affects impoverished regions of about 90 tropical and sub-tropical countries. Currently available antileishmanial therapies, particularly for visceral leishmaniasis, are severely limited, with treatment outcome depending on many factors, including the immune status of the patient, comorbidities, malnutrition, and socio-economic conditions in the patient\'s geographic location. There is an urgent need for new therapeutics, particularly new effective oral drugs, for visceral leishmaniasis. Despite the availability of the Leishmania genome sequence information and significant research into the biology of the parasites, antileishmanial drug development is hampered by the lack of knowledge about druggable targets in the parasite and difficulties in identifying the molecular targets of compounds that show activity. In this context, we analyzed recent progress in antileishmanial drug development programs, which take advantage of different powerful approaches, such as high-throughput screening of compound libraries, recent developments in genetic methods for assessing essentiality of parasite genes, and chemical, genetic, and proteomics-based target discovery and target validation methods.
摘要：
利什曼病,一种由至少20种利什曼原虫属单细胞寄生虫引起的复杂疾病，不成比例地影响了大约90个热带和亚热带国家的贫困地区。目前可用的抗利什曼虫疗法，特别是内脏利什曼病，受到严重限制，治疗结果取决于许多因素，包括病人的免疫状态,合并症,营养不良,以及患者地理位置的社会经济状况。迫切需要新的治疗方法，特别是新的有效口服药物，内脏利什曼病.尽管利什曼原虫基因组序列信息的可用性和对寄生虫生物学的大量研究，由于缺乏有关寄生虫中可药用靶标的知识以及难以识别具有活性的化合物的分子靶标，因此阻碍了抗利什曼虫药物的开发。在这种情况下，我们分析了抗利什曼酶药物开发计划的最新进展，利用不同的强大方法，如高通量筛选化合物文库，评估寄生虫基因重要性的遗传方法的最新进展，化学,遗传,以及基于蛋白质组学的靶标发现和靶标验证方法。
