Treating virus infections in mosquitoes â€" a novel strategy to prevent disease transmission

In the last decades, the global expansion of virus-transmitting mosquitoes, primarily Aedes aegypti and Aedes albopictus, has caused an unprecedented increase in epidemics of mosquito-borne viruses including dengue, Zika, and chikungunya. Currently, mosquito control with unspecific insecticides is still considered the most effective intervention method. However, the use of conventional insecticides leads to rapid selection of insecticide-resistant mosquitoes and causes substantial collateral damage to beneficial (pollinating) insects. Efficient virus transmission requires high virus levels in the mosquito. Hence, interference with virus replication in mosquitoes is expected to effectively interfere with virus transmission. I, therefore, propose an alternative transmission-blocking strategy that targets virus replication in mosquitoes using small-molecule inhibitors. I aim to identify active compounds by screening ~750 small-molecules for antiviral activity against dengue virus in mosquito cells. Hits from this screen will be further assessed for their potency to suppress virus replication and transmission in adult Aedes aegypti mosquitoes. This project will provide important proof of concept for the development of an active ingredient for a new generation of sugar-baited mosquito traps. My approach resolves the issue of insecticide resistance and provides a sustainable, pollinator-sparing, alternative to insecticidal components in sugar baits.