In silico Characterization of OBPs and ORs of Aedes aegypti to Screen Potential Attractants and Repellents for Vector Control Strategies

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.