Dengue and chikungunya viruses infect hundreds of millions of people each year, and there are no drugs against them. The main way to curb epidemics is to kill mosquitoes with insecticides, but insects develop resistance, and chemicals harm the environment. Alongside this work, the archive contains a study on mathematical modeling of dengue fever that treats the city as an organism and looks for patterns in the spread of the disease. Both works seek new ways to intervene in the virus transmission cycle, but this paper proposes not killing mosquitoes but treating them for the virus.
Aedes aegypti mosquitoes were offered a sugar solution with one of four antiviral drugs added: JNJ-A07, molnupiravir (MPV), NHC, or 4'-fluorouridine (4'FlU). First, isolated mosquito midguts were used to test which concentration of 4'FlU suppresses chikungunya virus. Then the mosquitoes were given the bait for three days before blood-borne infection and four days after. At 3, 7, and 14 days after infection, the amount of virus was measured in the body, head with wings, and legs, as well as in saliva, to assess the mosquito's ability to transmit the infection.
A bait with JNJ-A07 at a concentration of 20 µM reduced the proportion of mosquitoes infected with dengue virus from 87% to 3% at 14 days after infection. The spread of the virus from the midgut to other tissues fell from 100% to 0%. A bait with 4'FlU at a concentration of 200 µM reduced the proportion of mosquitoes infected with chikungunya by about one-third on days 3 and 14 after infection, and the amount of virus in the mosquito body decreased by 138, 513, and 355 times on days 3, 7, and 14, respectively. MPV and NHC produced no significant effect. The baits did not repel mosquitoes: the preference index remained positive (from 0.025 to 0.33). The impact on survival and reproduction was weak and depended on the drug and sex: NHC reduced female survival, and 4'FlU reduced male survival, but overall mortality was mainly explained by natural aging.
The work shows that antiviral drugs can be delivered to mosquitoes through sugar bait and thereby suppress the virus inside the vector without killing it. This differs from traditional insecticidal baits, which kill mosquitoes and create selection pressure for resistance. The neighboring study on mathematical modeling of dengue examines the spread of the disease at the population level, whereas this research acts at the level of an individual mosquito and the virus within it. This approach could reduce the risk of resistance and lessen environmental damage.
The next step is to test the baits in semi-field and field conditions, where mosquitoes have access to natural sugar sources and insect behavior differs from the laboratory. It is important to understand how often mosquitoes will visit the baits in nature and how stably the drugs persist in the sugar solution. It is also necessary to study the pharmacokinetics of the drugs in the mosquito body: how quickly they are excreted and which tissues they reach.
The results could be used to develop new control tools against vector mosquitoes in urban and rural areas where dengue and chikungunya fevers are common.
Conduct experiments in large cages with natural sugar sources, and then move to field trials in a limited area.
For virology and medical entomology, it remains an open question how exactly antiviral drugs are distributed and metabolized in mosquito tissues. Without these data, it is difficult to predict the effectiveness of baits in the field and to choose optimal dosages.
Aedes aegypti mosquitoes live about 27 days at 28°C, so in the 30-day survival experiment, a significant portion of mortality was natural rather than caused by the drugs.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.