Unpacking boxes: identification of novel inhibitors of malaria parasite invasion
s for growth and invasion were similar. Of these six inhibitors, two (MMV006931 and MMV024850) were found to directly block the invasion of mechanically purified merozoites. We sought to identify the protein targets of these compounds through resistance selection and subsequent whole genome sequencing. We were able to select parasites with robust resistance to MMV006931 but not MMV024850. Genome sequencing of clonal MMV006931-resistant parasites identified mutations in the P. falciparum sterol exporter PfNCR1, which helps eliminate excess cholesterol from the parasite's plasma membrane. By demonstrating that MMV006931 sensitises parasites to lysis by a sterol-dependent detergent, we confirmed that PfNCR1 is the likely target of MMV006931.
Authors
- Claudia B. G. Barnes
- Zahra Razook (ORCID: https://orcid.org/0009-0000-9630-6212)
- Brendan S. Crabb (ORCID: https://orcid.org/0000-0002-0480-5557)
- Paul R. Gilson (ORCID: https://orcid.org/0000-0001-8778-6795)
- Kirsty McCann (ORCID: https://orcid.org/0000-0002-2427-241X)
- Hayley E. Bullen (ORCID: https://orcid.org/0000-0003-4923-3019)
- Coralie Boulet (ORCID: https://orcid.org/0000-0002-5476-7800)
- Brad E. Sleebs (ORCID: https://orcid.org/0000-0001-9117-1048)
- Molly Parkyn Schneider (ORCID: https://orcid.org/0000-0002-5491-5455)
- Alyssa E. Barry (ORCID: https://orcid.org/0000-0002-1189-2310)
- Olivia D. Ventura
- Alysha H. Literski (ORCID: https://orcid.org/0009-0008-3439-9749)
Institutions
- Burnet Institute (AU)
- Deakin University (AU)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
Publication Details
- Journal
- International Journal for Parasitology Drugs and Drug Resistance
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1016/j.ijpddr.2026.100647
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Health and Medical Research Council