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10-Minute Presentation

Medical, Urban, and Veterinary Entomology

10-min: MUVE, Mosquito Physiology, Surveillance, and Control

Pantazines: Small molecules with sizable potential for reducing malaria parasite development in a globally invasive mosquito

Tuesday, November 11, 2025
10:48 AM - 11:00 AM Pacific
Location: Oregon Convention Center, B114, OCC
Oral Presentation
Plasmodium parasites must acquire nutrients like pantothenate (Pan) from their hosts for successful propagation. Pan is enzymatically converted to coenzyme A (CoA), an essential cofactor in many metabolic pathways. Mammalian Pan and CoA are acquired by blood-stage parasites, but mosquito stage parasites can only acquire Pan from the insect host and must synthesize their own CoA. In the CoA biosynthetic pathway, pantothenate kinase (PanK) is the rate-limiting enzyme and a target for human drug development. In previous studies, we leveraged Pan-dependency of parasites in the mosquito to demonstrate that the small molecule mammalian PanK activator or pantazine, PZ-2891, significantly restricted the development of the mouse parasite Plasmodium yoelii and the human parasite Plasmodium falciparum in A. stephensi. We recently tested two second-generation pantazines (PZ-3022 and PZ-3883) with improved stability and activity for their effect on Pan levels and infection-blocking activity in A. stephensi. We demonstrated that Pan levels of A. stephensi were significantly reduced at 24 h post-pantazine treatment compared to controls. In our infection assays, female mosquitoes were treated with PZ-3022 or PZ-3883 delivered via soaked cotton pads while controls received water only. After three days, treatment and control groups were allowed to feed on mice infected with P. yoelii or on blood with P. falciparum. Both pantazines significantly reduced midgut oocyst and salivary gland sporozoite infections at 10 d and 14 d post-infection, respectively, relative to control for both parasite species, suggesting that pantazines are promising transmission-blocking drug candidates.