Antivirals against arboviruses: Taking into account the mosquito vector

Arboviruses, viruses transmitted by mosquitoes or other arthropods, are a major burden for global health. They can cause severe diseases such as hemorrhagic fever, encephalitis and chronic arthritis. Despite the significant disease burden and widespread presence of these viruses, antiviral drugs are not available. One of the challenges for arbovirus antiviral drug development is the short viremia of arboviruses (< 1 week), requiring antiviral therapy to be initiated soon after the start of the infection. Therapeutic use of antiviral drugs will therefore be complicated, because an early diagnosis is currently almost impossible in the developing world, where most of the infections occur. Pre-exposure prophylaxis of travelers and household members of an infected patient has been proposed as an alternative strategy, but also comes with challenges. There is thus a clear need for new strategies to combat arbovirus infections. The goal of this PhD project is to gain insights in the interplay between antiviral drugs and arbovirus replication in mosquitoes. First, we will screen a library of compounds with antiviral activity against arboviruses in mosquito cells to select compounds that are effective in the mosquito host. Consequently, potent antiviral compounds will be delivered to mosquitoes by different routes to study whether these compounds are able to reduce arbovirus replication in the mosquito. A significant decrease in arbovirus infection in the mosquito might result in reduced transmission to humans/animals. The use of antiviral drugs as transmission-blocking agents at the level of the mosquito could thus be a new concept in the fight against arbovirus infections.