被忽视的热带疾病
药物发现
利什曼病
药品
热带疾病
清脆的
生物
抗药性
计算生物学
药物开发
非洲锥虫病
利什曼原虫
疾病
医学
生物信息学
药理学
锥虫病
计算机科学
免疫学
病理
遗传学
基因
万维网
寄生虫寄主
作者
Fernando Altamura,Rishi Rajesh,Carolina Moura Costa Catta-Preta,Nilmar Silvio Moretti,Igor Cestari
摘要
Human trypanosomiasis and leishmaniasis are vector-borne neglected tropical diseases caused by infection with the protozoan parasites Trypanosoma spp. and Leishmania spp., respectively. Once restricted to endemic areas, these diseases are now distributed worldwide due to human migration, climate change, and anthropogenic disturbance, causing significant health and economic burden globally. The current chemotherapy used to treat these diseases has limited efficacy, and drug resistance is spreading. Hence, new drugs are urgently needed. Phenotypic compound screenings have prevailed as the leading method to discover new drug candidates against these diseases. However, the publication of the complete genome sequences of multiple strains, advances in the application of CRISPR/Cas9 technology, and in vivo bioluminescence-based imaging have set the stage for advancing target-based drug discovery. This review analyses the limitations of the narrow pool of available drugs presently used for treating these diseases. It describes the current drug-based clinical trials highlighting the most promising leads. Furthermore, the review presents a focused discussion on the most important biological and pharmacological challenges that target-based drug discovery programs must overcome to advance drug candidates. Finally, it examines the advantages and limitations of modern research tools designed to identify and validate essential genes as drug targets, including genomic editing applications and in vivo imaging.
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