Tarsal exposure to atovaquone inhibits chikungunya virus transmission by Aedes aegypti mosquitoes, but not the transmission of Zika virus

Abstract

The antimalarial drug atovaquone was recently reported to inhibit the in vitro replication of different arboviruses, including chikungunya virus (CHIKV) and Zika virus (ZIKV). Furthermore, atovaquone was shown to block Plasmodium parasite transmission by Anopheles mosquitoes when the mosquitoes were exposed to low concentrations on treated surfaces (i.e. tarsal exposure). Therefore, we evaluated the anti-CHIKV and -ZIKV effects of atovaquone via tarsal exposure in Aedes aegypti mosquitoes. We first confirmed that atovaquone exerted a dose-dependent antiviral effect on CHIKV and ZIKV replication in mosquito-derived cells. The modest antiviral effect could be rescued by adding exogenous uridine. Next, we assessed the effect of tarsal exposure to atovaquone on the fitness of Ae. aegypti. Concentrations up to 100 μmol/m² did not affect the fecundity and egg-hatching rate. No significant effect on mosquito survival was observed when mosquitoes were exposed to concentrations up to 25 μmol/m². To evaluate the antiviral effect of atovaquone against CHIKV, we exposed female mosquitoes to 100 μmol/m² atovaquone for 1h, after which the mosquitoes were immediately infected with CHIKV or ZIKV via bloodmeal. Atovaquone did not significantly reduce ZIKV or CHIKV infection in Ae. aegypti, but successfully blocked the transmission of CHIKV in saliva. Tarsal exposure to antiviral drugs could therefore be a potential new strategy to reduce virus transmission by mosquitoes.

Keywords: Aedes aegypti; Atovaquone; Chikungunya virus; Tarsal exposure; Virus transmission; Zika virus.