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Atovaquone-venturicidin A combination is synergistic against Plasmodium falciparum

Hauser, D.; Sax, S.; Keller, S.; Cal, M.; Kaiser, M.; Maser, P.

2025-08-19 microbiology
10.1101/2025.08.18.670846 bioRxiv
Show abstract

We report the synergistic interaction between the complex III inhibitor atovaquone and an ATP synthase inhibitor, venturicidin A, against Plasmodium falciparum. Our results suggest the simultaneous inhibition of the parasites primary and alternative pathways for generating the mitochondrial membrane potential to be responsible for this phenomenon, whereby the alternative pathway relies on ATP synthase running in reverse mode. We hypothesize that the synergistic interaction between atovaquone and proguanil could follow a similar mechanism.

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