Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including infectivity to the human host. As a result of advances in the knowledge of the structural aspects of cysteine proteases and their role in disease physiopathology, inhibition of these enzymes by small molecules has been demonstrated to be a worthwhile approach to trypanosomatid drug research. This review provides an update on drug discovery strategies targeting the cysteine peptidases cruzain from Trypanosoma cruzi and rhodesain and cathepsin B from Trypanosoma brucei. Given that current chemotherapy for Chagas disease and human African trypanosomiasis has several drawbacks, cysteine proteases will continue to be actively pursued as valuable molecular targets in trypanosomatid disease drug discovery efforts.

南美锥虫病和人类非洲锥虫病分别是拉丁美洲和非洲的地方病，目前尚无有效和安全的治疗方法。药物发现的努力集中在来自这些原生动物的几种酶上，其中半胱氨酸蛋白酶已被确认为药理学干预的分子靶标。这些酶在锥虫寄生虫的整个生命周期中表达，并且对许多生物学过程（包括对人宿主的感染性）都是必不可少的。由于对半胱氨酸蛋白酶的结构方面及其在疾病生理病理学中的作用的了解的不断发展，已证明用小分子抑制这些酶是锥虫病药物研究的一种有价值的方法。克氏锥虫和rhodesain和组织蛋白酶B从布氏锥虫。鉴于当前用于查加斯病和人类非洲锥虫病的化学疗法有几个缺点，半胱氨酸蛋白酶将继续作为锥虫病疾病药物发现工作中有价值的分子靶标而被积极追求。