Anti-Wolbachia drugs for filariasis



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.

[img] 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
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