Mammalian-targeted antiviral peptide reduces dengue virus type 1 infection in Aedes aegypti

Dengue virus is the most important arbovirus for public health worldwide. Aedes aegypti is the DENV primary vector and acquires the virus during blood meal from a viremic human. BCN0941 is a structure-based designed antiviral peptide that inhibits early stages of DENV infection in mammalian cells [WO2015131858A2]. Studies of structure-activity relationship indicate that the molecular target of the antiviral activity of BCN0941 is the Low-density lipoprotein receptor related protein-1 (LRP1), an evolutionary conserved receptor that we have identified as putative DENV receptor in mammalian cells. In this work, we evaluated the antiviral activity of BCN0941 peptide against DENV serotype 1 in mosquito cells. In vitro assays were performed in cell lines C6/36 (Aedes albopictus) and Aag2 (Aedes aegypti). The antiviral activity in vivo in a metapopulation of field-collected A. aegypti mosquitoes was also evaluated. BCN0941 peptide exhibited the capacity to decrease viral infection in both experimental set up, in vivo and in vitro, up to a 50 % and 60 % of the treatment controls respectively, as determined by immunofluorescence. BCN0941 may be an effective DENV transmission-blocking drug due to its dual action in decreasing the viral load in infected people and the mosquito vector.