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Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches
The neglected tropical disease (NTD) leishmaniasis is the collective name given to a diverse group of illnesses caused by ~20 species belonging to the genus Leishmania, a majority of which are vector borne and associated with complex life cycles that cause immense health, social, and economic burden...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9414883/ https://www.ncbi.nlm.nih.gov/pubmed/36015070 http://dx.doi.org/10.3390/pathogens11080950 |
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author | Soni, Mohini Pratap, J. Venkatesh |
author_facet | Soni, Mohini Pratap, J. Venkatesh |
author_sort | Soni, Mohini |
collection | PubMed |
description | The neglected tropical disease (NTD) leishmaniasis is the collective name given to a diverse group of illnesses caused by ~20 species belonging to the genus Leishmania, a majority of which are vector borne and associated with complex life cycles that cause immense health, social, and economic burdens locally, but individually are not a major global health priority. Therapeutic approaches against leishmaniasis have various inadequacies including drug resistance and a lack of effective control and eradication of the disease spread. Therefore, the development of a rationale-driven, target based approaches towards novel therapeutics against leishmaniasis is an emergent need. The utilization of Artificial Intelligence/Machine Learning methods, which have made significant advances in drug discovery applications, would benefit the discovery process. In this review, following a summary of the disease epidemiology and available therapies, we consider three important leishmanial metabolic pathways that can be attractive targets for a structure-based drug discovery approach towards the development of novel anti-leishmanials. The folate biosynthesis pathway is critical, as Leishmania is auxotrophic for folates that are essential in many metabolic pathways. Leishmania can not synthesize purines de novo, and salvage them from the host, making the purine salvage pathway an attractive target for novel therapeutics. Leishmania also possesses an organelle glycosome, evolutionarily related to peroxisomes of higher eukaryotes, which is essential for the survival of the parasite. Research towards therapeutics is underway against enzymes from the first two pathways, while the third is as yet unexplored. |
format | Online Article Text |
id | pubmed-9414883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94148832022-08-27 Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches Soni, Mohini Pratap, J. Venkatesh Pathogens Review The neglected tropical disease (NTD) leishmaniasis is the collective name given to a diverse group of illnesses caused by ~20 species belonging to the genus Leishmania, a majority of which are vector borne and associated with complex life cycles that cause immense health, social, and economic burdens locally, but individually are not a major global health priority. Therapeutic approaches against leishmaniasis have various inadequacies including drug resistance and a lack of effective control and eradication of the disease spread. Therefore, the development of a rationale-driven, target based approaches towards novel therapeutics against leishmaniasis is an emergent need. The utilization of Artificial Intelligence/Machine Learning methods, which have made significant advances in drug discovery applications, would benefit the discovery process. In this review, following a summary of the disease epidemiology and available therapies, we consider three important leishmanial metabolic pathways that can be attractive targets for a structure-based drug discovery approach towards the development of novel anti-leishmanials. The folate biosynthesis pathway is critical, as Leishmania is auxotrophic for folates that are essential in many metabolic pathways. Leishmania can not synthesize purines de novo, and salvage them from the host, making the purine salvage pathway an attractive target for novel therapeutics. Leishmania also possesses an organelle glycosome, evolutionarily related to peroxisomes of higher eukaryotes, which is essential for the survival of the parasite. Research towards therapeutics is underway against enzymes from the first two pathways, while the third is as yet unexplored. MDPI 2022-08-22 /pmc/articles/PMC9414883/ /pubmed/36015070 http://dx.doi.org/10.3390/pathogens11080950 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Soni, Mohini Pratap, J. Venkatesh Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches |
title | Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches |
title_full | Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches |
title_fullStr | Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches |
title_full_unstemmed | Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches |
title_short | Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches |
title_sort | development of novel anti-leishmanials: the case for structure-based approaches |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9414883/ https://www.ncbi.nlm.nih.gov/pubmed/36015070 http://dx.doi.org/10.3390/pathogens11080950 |
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