KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, B-3000, Leuven, Belgium.
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, B-3000, Leuven, Belgium; Laboratoire d'Entomologie Fondamentale et Appliquée, Université Joseph Ki-Zerbo, Burkina Faso.
Antiviral Res. 2023 Sep;217:105694. doi: 10.1016/j.antiviral.2023.105694. Epub 2023 Aug 1.
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/m 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/m. To evaluate the antiviral effect of atovaquone against CHIKV, we exposed female mosquitoes to 100 μmol/m 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.
抗疟药物阿托伐醌最近被报道可抑制不同虫媒病毒的体外复制，包括基孔肯雅病毒（CHIKV）和寨卡病毒（ZIKV）。此外，当蚊子接触到处理过的表面（即跗节暴露）上的低浓度药物时，阿托伐醌被证明可阻止疟原虫寄生虫通过疟蚊传播。因此，我们通过蚊子跗节暴露评估了阿托伐醌对 CHIKV 和 ZIKV 的抗虫效果。我们首先证实阿托伐醌对蚊源细胞中 CHIKV 和 ZIKV 的复制具有剂量依赖性的抗病毒作用。适度的抗病毒作用可以通过添加外源性尿苷得到挽救。接下来，我们评估了阿托伐醌跗节暴露对埃及伊蚊适应性的影响。浓度高达 100μmol/m 时，不会影响其繁殖力和卵孵化率。当蚊子暴露于浓度高达 25μmol/m 时，对蚊子存活率没有显著影响。为了评估阿托伐醌对 CHIKV 的抗病毒作用，我们用 100μmol/m 阿托伐醌处理雌性蚊子 1 小时，然后立即通过血餐感染 CHIKV 或 ZIKV。阿托伐醌并未显著降低 Ae. aegypti 中的 ZIKV 或 CHIKV 感染，但成功阻断了 CHIKV 在唾液中的传播。因此，蚊子跗节暴露于抗病毒药物可能是减少蚊子传播病毒的一种潜在新策略。
