Description
Title: New Anti-Leishmanial Drug Development: The Case for Structure-Based Methods
Abstract: Leishmaniasis, also known as neglected tropical disease (NTD) leishmaniasis, refers to a diverse group of diseases caused by about 20 species of the genus Leishmania. The majority of these diseases are vector-borne and have complex life cycles that place significant local health, social, and economic burdens on communities, but they are not considered to be major global health priorities individually. Leishmaniasis treatment methods have a number of shortcomings, including drug resistance and a lack of efficient measures to stop the spread of the disease. Therefore, there is an urgent need for the creation of target-based, reasoning-driven approaches to novel therapeutics against leishmaniasis. The process of discovery would benefit from the use of artificial intelligence/machine learning techniques, which have made significant strides in drug discovery applications. In this review, we consider three significant leishmanial metabolic pathways that can be appealing targets for a structure-based drug discovery approach towards the development of novel anti-leishmanials, following a summary of the disease epidemiology and available therapies. Given that Leishmania is an auxotroph for folates, which are necessary in numerous metabolic pathways, the folate biosynthesis pathway is crucial. Purine salvage is a prime target for novel therapeutics because Leishmania cannot synthesize purines from scratch and can only obtain them from the host. Additionally, Leishmania has an organelle called a glycosome that is crucial to the parasite’s survival and has evolutionary ties to higher eukaryotes’ peroxisomes. The first two pathways’ enzymes are the subject of ongoing therapeutic research; the third is still unexplored.
Keywords: leishmaniasis; neglected tropical disease; purine salvage pathway; folate biosynthesis pathway; peroxisomal pathway; structure-based drug design
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Biology
Writer Experience: 20+ Years
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