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Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections
The intracellular bacteria now known as Wolbachia were first described in filarial worms in the 1970s, but the idea of Wolbachia being used as a macrofilaricidal target did not gain wide attention until the early 2000s, with research in filariae suggesting the requirement of worms for the endosymbio...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789823/ https://www.ncbi.nlm.nih.gov/pubmed/31323841 http://dx.doi.org/10.3390/tropicalmed4030108 |
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author | Bakowski, Malina A. McNamara, Case W. |
author_facet | Bakowski, Malina A. McNamara, Case W. |
author_sort | Bakowski, Malina A. |
collection | PubMed |
description | The intracellular bacteria now known as Wolbachia were first described in filarial worms in the 1970s, but the idea of Wolbachia being used as a macrofilaricidal target did not gain wide attention until the early 2000s, with research in filariae suggesting the requirement of worms for the endosymbiont. This new-found interest prompted the eventual organization of the Anti-Wolbachia Consortium (A-WOL) at the Liverpool School of Tropical Medicine, who, among others have been active in the field of antiwolbachial drug discovery to treat filarial infections. Clinical proof of concept studies using doxycycline demonstrated the utility of the antiwolbachial therapy, but efficacious treatments were of long duration and not safe for all infected. With the advance of robotics, automation, and high-speed computing, the search for superior antiwolbachials shifted away from smaller studies with a select number of antibiotics to high-throughput screening approaches, centered largely around cell-based phenotypic screens due to the rather limited knowledge about, and tools available to manipulate, this bacterium. A concomitant effort was put towards developing validation approaches and in vivo models supporting drug discovery efforts. In this review, we summarize the strategies behind and outcomes of recent large phenotypic screens published within the last 5 years, hit compound validation approaches and promising candidates with profiles superior to doxycycline, including ones positioned to advance into clinical trials for treatment of filarial worm infections. |
format | Online Article Text |
id | pubmed-6789823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67898232019-10-16 Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections Bakowski, Malina A. McNamara, Case W. Trop Med Infect Dis Review The intracellular bacteria now known as Wolbachia were first described in filarial worms in the 1970s, but the idea of Wolbachia being used as a macrofilaricidal target did not gain wide attention until the early 2000s, with research in filariae suggesting the requirement of worms for the endosymbiont. This new-found interest prompted the eventual organization of the Anti-Wolbachia Consortium (A-WOL) at the Liverpool School of Tropical Medicine, who, among others have been active in the field of antiwolbachial drug discovery to treat filarial infections. Clinical proof of concept studies using doxycycline demonstrated the utility of the antiwolbachial therapy, but efficacious treatments were of long duration and not safe for all infected. With the advance of robotics, automation, and high-speed computing, the search for superior antiwolbachials shifted away from smaller studies with a select number of antibiotics to high-throughput screening approaches, centered largely around cell-based phenotypic screens due to the rather limited knowledge about, and tools available to manipulate, this bacterium. A concomitant effort was put towards developing validation approaches and in vivo models supporting drug discovery efforts. In this review, we summarize the strategies behind and outcomes of recent large phenotypic screens published within the last 5 years, hit compound validation approaches and promising candidates with profiles superior to doxycycline, including ones positioned to advance into clinical trials for treatment of filarial worm infections. MDPI 2019-07-18 /pmc/articles/PMC6789823/ /pubmed/31323841 http://dx.doi.org/10.3390/tropicalmed4030108 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Bakowski, Malina A. McNamara, Case W. Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections |
title | Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections |
title_full | Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections |
title_fullStr | Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections |
title_full_unstemmed | Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections |
title_short | Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections |
title_sort | advances in antiwolbachial drug discovery for treatment of parasitic filarial worm infections |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789823/ https://www.ncbi.nlm.nih.gov/pubmed/31323841 http://dx.doi.org/10.3390/tropicalmed4030108 |
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