Anti-Wolbachia drugs for filariasis

Kelly Johnston; W. David Hong; Joseph Turner; Paul M. O'Neill; Steve Ward; Mark Taylor

doi:10.1016/j.pt.2021.06.004

Anti-Wolbachia drugs for filariasis

Kelly Johnston, W. David Hong, Joseph Turner, Paul M. O'Neill, Steve Ward, Mark Taylor

University of Liverpool

Research output: Contribution to journal › Review article › peer-review

33 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1068-1081
Number of pages	14
Journal	Trends In Parasitology
Volume	37
Issue number	12
Early online date	3 Jul 2021
DOIs	https://doi.org/10.1016/j.pt.2021.06.004
Publication status	Published - 1 Dec 2021

Keywords

drug discovery
lymphatic filariasis
onchocerciasis
Wolbachia

Access to Document

10.1016/j.pt.2021.06.004

Johnston WolbachiaReview Manuscript Revision CLEANAccepted author manuscript, 218 KB

Cite this

@article{f2af34cb8d6f4f57aef223cc4ac43fef,

title = "Anti-Wolbachia drugs for filariasis",

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.",

keywords = "drug discovery, lymphatic filariasis, onchocerciasis, Wolbachia",

author = "Kelly Johnston and Hong, \{W. David\} and Joseph Turner and O'Neill, \{Paul M.\} and Steve Ward and Mark Taylor",

year = "2021",

month = dec,

day = "1",

doi = "10.1016/j.pt.2021.06.004",

language = "English",

volume = "37",

pages = "1068--1081",

journal = "Trends In Parasitology",

issn = "1471-4922",

publisher = "Elsevier Ltd",

number = "12",

}

TY - JOUR

T1 - Anti-Wolbachia drugs for filariasis

AU - Johnston, Kelly

AU - Hong, W. David

AU - Turner, Joseph

AU - O'Neill, Paul M.

AU - Ward, Steve

AU - Taylor, Mark

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

KW - drug discovery

KW - lymphatic filariasis

KW - onchocerciasis

KW - Wolbachia

U2 - 10.1016/j.pt.2021.06.004

DO - 10.1016/j.pt.2021.06.004

M3 - Review article

SN - 1471-4922

VL - 37

SP - 1068

EP - 1081

JO - Trends In Parasitology

JF - Trends In Parasitology

IS - 12

ER -

Anti-Wolbachia drugs for filariasis

Abstract

Keywords

Access to Document

Fingerprint

Cite this