Industrial scale high-throughput screening delivers multiple fast acting macrofilaricides
- Clare, Rachel H
- Bardelle, Catherine
- Harper, Paul
- Hong, W David
- Borjesson, Ulf
- Johnston, Kelly L
- Collier, Matthew
- Myhill, Laura
- Cassidy, Andrew
- Plant, Darren
- Plant, Helen
- Clark, Roger
- Cook, Darren AN
- Steven, Andrew
- Archer, John
- McGillan, Paul
- Charoensutthivarakul, Sitthivut
- Bibby, Jaclyn
- Sharma, Raman
- Nixon, Gemma L
- Slatko, Barton E
- Cantin, Lindsey
- Wu, Bo
- Turner, Joseph
- Ford, Louise
- Rich, Kirsty
- Wigglesworth, Mark
- Berry, Neil G
- O'Neill, Paul M
- Taylor, Mark J
- Ward, Stephen A
DOIAbstract
Nematodes causing lymphatic filariasis and onchocerciasis rely on their bacterial endosymbiont, Wolbachia, for survival and fecundity, making Wolbachia a promising therapeutic target. Here we perform a high-throughput screen of AstraZeneca’s 1.3 million in-house compound library and identify 5 novel chemotypes with faster in vitro kill rates (<2 days) than existing anti-Wolbachia drugs that cure onchocerciasis and lymphatic filariasis. This industrial scale anthelmintic neglected tropical disease (NTD) screening campaign is the result of a partnership between the Anti-Wolbachia consortium (A∙WOL) and AstraZeneca. The campaign was informed throughout by rational prioritisation and triage of compounds using cheminformatics to balance chemical...
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