Plasmodium falciparum proteases as new drug targets with special focus on metalloproteases

IF 1.4 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology Pub Date : 2024-03-29 DOI:10.1016/j.molbiopara.2024.111617

Prabhash Jyoti Mahanta, Kimjolly Lhouvum

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引用次数: 0

Abstract

Malaria poses a significant global health threat particularly due to the prevalence of Plasmodium falciparum infection. With the emergence of parasite resistance to existing drugs including the recently discovered artemisinin, ongoing research seeks novel therapeutic avenues within the malaria parasite. Proteases are promising drug targets due to their essential roles in parasite biology, including hemoglobin digestion, merozoite invasion, and egress. While exploring the genomic landscape of Plasmodium falciparum, it has been revealed that there are 92 predicted proteases, with only approximately 14 of them having been characterized. These proteases are further distributed among 26 families grouped into five clans: aspartic proteases, cysteine proteases, metalloproteases, serine proteases, and threonine proteases. Focus on metalloprotease class shows further role in organelle processing for mitochondria and apicoplasts suggesting the potential of metalloproteases as viable drug targets. Holistic understanding of the parasite intricate life cycle and identification of potential drug targets are essential for developing effective therapeutic strategies against malaria and mitigating its devastating global impact.

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恶性疟原虫蛋白酶作为新的药物靶点，特别关注金属蛋白酶。

疟疾对全球健康构成重大威胁，特别是由于恶性疟原虫感染的流行。随着寄生虫对现有药物（包括最近发现的青蒿素）产生抗药性，目前的研究正在疟疾寄生虫体内寻找新的治疗途径。蛋白酶在寄生虫生物学（包括血红蛋白消化、裂殖体侵入和排出）中发挥着重要作用，因此是很有希望的药物靶点。在探索恶性疟原虫的基因组图谱时，发现有 92 种预测的蛋白酶，其中只有约 14 种已被鉴定。这些蛋白酶进一步分布在 26 个家族中，分为天冬氨酸蛋白酶、半胱氨酸蛋白酶、金属蛋白酶、丝氨酸蛋白酶和苏氨酸蛋白酶五大类。对金属蛋白酶类的关注进一步显示了金属蛋白酶在线粒体和细胞质处理过程中的作用，这表明金属蛋白酶有可能成为可行的药物靶点。全面了解寄生虫错综复杂的生命周期并确定潜在的药物靶点，对于制定有效的疟疾治疗策略和减轻其对全球的破坏性影响至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and biochemical parasitology 医学-寄生虫学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

63 days

期刊介绍： The journal provides a medium for rapid publication of investigations of the molecular biology and biochemistry of parasitic protozoa and helminths and their interactions with both the definitive and intermediate host. The main subject areas covered are: • the structure, biosynthesis, degradation, properties and function of DNA, RNA, proteins, lipids, carbohydrates and small molecular-weight substances • intermediary metabolism and bioenergetics • drug target characterization and the mode of action of antiparasitic drugs • molecular and biochemical aspects of membrane structure and function • host-parasite relationships that focus on the parasite, particularly as related to specific parasite molecules. • analysis of genes and genome structure, function and expression • analysis of variation in parasite populations relevant to genetic exchange, pathogenesis, drug and vaccine target characterization, and drug resistance. • parasite protein trafficking, organelle biogenesis, and cellular structure especially with reference to the roles of specific molecules • parasite programmed cell death, development, and cell division at the molecular level.