Abstract:
Dengue virus, transmitted by Aedes aegypti, causes about 100 million infections
leading to hospitalization of 500,000 patients. Like other insects, olfactory system of
Ae. aegypti, a dengue vector, consists of odorant binding proteins (OBPs) and odorant
receptor (ORs). Being the vital components, these are crucial to the feeding,
oviposition, and mating because of their involvement in sensing the olfactory cues. In
this study, subcellular localization, signal peptide and three-dimensional structures of
selective fifteen OBPs and five ORs of Ae. aegypti were predicted utilizing various
computational tools. Furthermore, commercially available attractants and repellents
were assessed for the development of pipeline to identify the novel compounds as
attractants and repellents. Molecular docking was carried out to find the binding
energies of attractants and repellents with the OBPs and ORs. This study has designed
a novel pipeline to identify novel attractants and repellents for the first time. Three dimensional structure of classic, atypical and plus-C OBPs highlighted the structural
difference in these subclasses of OBPs. Assessment of ORs structures revealed that
these consist of seven transmembrane helices having N-terminal and C-terminal
facing intracellular and extracellular sides, respectively, of dendritic membrane. Using
these novel findings, three potential attractants and repellents, having no toxic and
mutagenic properties, were identified via designed pipeline and molecular docking.
This study provides the novel insights into the olfactory mechanisms of Ae. aegypti
and develops a pipeline to identify the attractants and repellents to be used in
integrated mosquito management (IMM), push & pull, and lure & kill strategies for
mosquito control.
