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Anti-Wolbachia drugs for filariasis

Johnston, Kelly, Hong, W. David, Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476, O’Neill, Paul M., Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 (2021) 'Anti-Wolbachia drugs for filariasis'. Trends in Parasitology. (In Press)

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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
Subjects: QW Microbiology and Immunology > Bacteria > QW 150 Proteobacteria. Rickettsiaceae, Wolbachia
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1016/j.pt.2021.06.004
Depositing User: Marie Hatton
Date Deposited: 23 Aug 2021 09:45
Last Modified: 23 Aug 2021 09:45
URI: https://archive.lstmed.ac.uk/id/eprint/18716

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