Amity Institute of Biotechnology, Amity University Rajasthan, Kant Kalwar, NH-11C, Jaipur-Delhi Highway, Jaipur, India.
Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, India.
Microbiol Res. 2021 Aug;249:126784. doi: 10.1016/j.micres.2021.126784. Epub 2021 May 6.
Millions of people worldwide lie at the risk of parasitic protozoic infections that kill over a million people each year. The rising inefficacy of conventional therapeutics to combat these diseases, mainly due to the development of drug resistance to a handful of available licensed options contributes substantially to the rising burden of these ailments. Cysteine proteases are omnipresent enzymes that are critically implicated in the pathogenesis of protozoic infections. Despite their significance and druggability, cysteine proteases as therapeutic targets have not yet been translated into the clinic. The review presents the significance of cysteine proteases of members of the genera Plasmodium, Entamoeba, and Leishmania, known to cause Malaria, Amoebiasis, and Leishmaniasis, respectively, the protozoic diseases with the highest morbidity and mortality. Further, projecting them as targets for molecular tools like the CRISPR-Cas technology for favorable manipulation, exploration of obscure genomes, and achieving a better insight into protozoic functioning. Overcoming the hurdles that prevent us from gaining a better insight into the functioning of these enzymes in protozoic systems is a necessity. Managing the burden of parasitic protozoic infections pivotally depends upon the betterment of molecular tools and therapeutic concepts that will pave the path to an array of diagnostic and therapeutic applications.
全世界数百万人面临寄生虫原生动物感染的风险，每年有超过 100 万人因此死亡。由于对少数现有许可药物的耐药性的发展，传统疗法对抗这些疾病的效果不断下降，这在很大程度上导致了这些疾病负担的增加。半胱氨酸蛋白酶是普遍存在的酶，它们在原生动物感染的发病机制中起着关键作用。尽管半胱氨酸蛋白酶具有重要意义和可成药性，但作为治疗靶点的半胱氨酸蛋白酶尚未转化为临床应用。该综述介绍了导致疟疾、阿米巴病和利什曼病的寄生虫属成员的半胱氨酸蛋白酶的重要性，分别是发病率和死亡率最高的原生动物疾病。此外，还将它们作为分子工具（如 CRISPR-Cas 技术）的靶点，用于有利的操作、探索未知的基因组，并深入了解原生动物的功能。克服阻碍我们更好地了解原生动物系统中这些酶功能的障碍是必要的。管理寄生虫原生动物感染的负担主要取决于分子工具和治疗概念的改进，这将为一系列诊断和治疗应用铺平道路。
