ArticlePLoS biology2023
Sulfonylpiperazine compounds prevent Plasmodium falciparum invasion of red blood cells through interference with actin-1/profilin dynamics.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
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- An essential adaptor for apicoplast fission and inheritance in malaria parasites.Nature communications · 2025Article
- An Essential Adaptor for Apicoplast Fission and Inheritance in Malaria Parasites.bioRxiv : the preprint server for biology · 2025Article
- Optimization and Characterization of the Antimalarial Activity ofJournal of medicinal chemistry · 2025Article
- Fungal-derived methyldeoxaphomins targetProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Applications of CRISPR in Parasitology.Current pharmaceutical biotechnology · 2025Review
- An adaptable, fit-for-purpose screening approach with high-throughput capability to determine speed of action and stage specificity of anti-malarial compounds.Antimicrobial agents and chemotherapy · 2024Article
- Antimalarial efficacy test of the aqueous crude leaf extract of Coriandrum sativum Linn.: an in vivo multiple model experimental study in mice infected with Plasmodium berghei.BMC complementary medicine and therapies · 2024Article
- Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.Nature communications · 2024Article
- Three Rounds of Read Correction Significantly Improve Eukaryotic Protein Detection in ONT Reads.Microorganisms · 2024Article
- A Pyridyl-Furan Series Developed from the Open Global Health Library Block Red Blood Cell Invasion and Protein Trafficking inACS infectious diseases · 2023Article
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With emerging resistance to frontline treatments, it is vital that new antimalarial drugs are identified to target Plasmodium falciparum. We have recently described a compound, MMV020291, as a specific inhibitor of red blood cell (RBC) invasion, and have generated analogues with improved potency. Here, we generated resistance to MMV020291 and performed whole genome sequencing of 3 MMV020291-resistant populations. This revealed 3 nonsynonymous single nucleotide polymorphisms in 2 genes; 2 in profilin (N154Y, K124N) and a third one in actin-1 (M356L). Using CRISPR-Cas9, we engineered these mutations into wild-type parasites, which rendered them resistant to MMV020291. We demonstrate that MMV020291 reduces actin polymerisation that is required by the merozoite stage parasites to invade RBCs. Additionally, the series inhibits the actin-1-dependent process of apicoplast segregation, leading to a delayed death phenotype. In vitro cosedimentation experiments using recombinant P. falciparum proteins indicate that potent MMV020291 analogues disrupt the formation of filamentous actin in the presence of profilin. Altogether, this study identifies the first compound series interfering with the actin-1/profilin interaction in P. falciparum and paves the way for future antimalarial development against the highly dynamic process of actin polymerisation.
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