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

Abstract

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.