Journal article

Low cost whole-organism screening of compounds for anthelmintic activity

Sarah Preston, Abdul Jabbar, Cameron Nowell, Anja Joachim, Baerbel Ruttkowski, Jonathan Baell, Tony Cardno, Pasi K Korhonen, David Piedrafita, Brendan RE Ansell, Aaron R Jex, Andreas Hofmann, Robin B Gasser

INTERNATIONAL JOURNAL FOR PARASITOLOGY | ELSEVIER SCI LTD | Published : 2015

Abstract

Due to major problems with drug resistance in parasitic nematodes of animals, there is a substantial need and excellent opportunities to develop new anthelmintics via genomic-guided and/or repurposing approaches. In the present study, we established a practical and cost-effective whole-organism assay for the in vitro-screening of compounds for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm). The assay is based on the use of exsheathed L3 (xL3) and L4 stages of H. contortus of small ruminants (sheep and goats). Using this assay, we screened a panel of 522 well-curated kinase inhibitors (GlaxoSmithKline, USA; code: PKIS2) for activity against H. cont..

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Grants

Awarded by Victoria Life Sciences Computation Initiative, Australia (VLSCI) on its Peak Computing Facility at the University of Melbourne, Australia, an initiative of the Victorian Government, Australia


Funding Acknowledgements

The present study was funded by the National Health and Medical Research Council of Australia (NHMRC) and the Australian Research Council (ARC), and supported by a Victoria Life Sciences Computation Initiative, Australia (VLSCI; grant number VR0007) on its Peak Computing Facility at the University of Melbourne, Australia, an initiative of the Victorian Government, Australia. Animal ethics approval (AEC no. 0707258) was granted by The University of Melbourne. We also thank Professor Christian Doerig (Monash University, Melbourne, Australia) for introducing us to Drs David Drewry and Bill Zurcher (GlaxoSmithKline, USA) who kindly provided us with the PKIS2 compounds.