Johnston, Kelly L, Hong, W David, Turner, Joseph D, O'Neill, Paul M ORCID: 0000-0003-4338-0317, Ward, Stephen A and Taylor, Mark J
(2021)
Anti-Wolbachia drugs for filariasis.
TRENDS IN PARASITOLOGY, 37 (12).
pp. 1068-1081.
Text
Johnston_WolbachiaReview_Manuscript_Revision_CLEAN.docx - Author Accepted Manuscript Download (222kB) |
Abstract
The mutualistic association between Wolbachia endosymbionts and their filarial nematode hosts has been exploited as a validated drug target delivering macrofilaricidal outcomes. Limitations of existing antibiotics to scale-up have driven the search for new drugs, which are effective in shorter regimens of 7 days or less. Here, we review the last 14 years of anti-Wolbachia drug discovery by the anti-Wolbachia (A·WOL) consortium, which has screened more than two million compounds, delivering thousands of hit compounds. Refined screening models integrated with robust pharmacokinetic/pharmacodynamic (PK/PD) driven optimisation and selection strategies have delivered the first two drug candidates specifically designed to target Wolbachia. AWZ1066S and ABBV-4083 are currently progressing through clinical trials with the aim of delivering safe and effective macrofilaricides to support the elimination of onchocerciasis and lymphatic filariasis.
Item Type: | Article |
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Uncontrolled Keywords: | Humans, Wolbachia, Nematode Infections, Elephantiasis, Filarial, Onchocerciasis, Anti-Bacterial Agents, Drug Discovery |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology > School of Life Sciences Faculty of Science and Engineering > School of Physical Sciences |
Depositing User: | Symplectic Admin |
Date Deposited: | 13 Jul 2021 07:20 |
Last Modified: | 04 Jul 2023 14:24 |
DOI: | 10.1016/j.pt.2021.06.004 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3129754 |