Atovaquone-venturicidin A combination is synergistic against Plasmodium falciparum

2025 · doi:10.1101/2025.08.18.670846
preprint OA: gold CC-BY-NC-ND-4.0
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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 parasite’s 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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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 parasite’s 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. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

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License: CC-BY-NC-ND-4.0