A Combined Computational Methodology for the Discovery of Hit Compounds with Putative Insect Repellency Properties

Mosquitoes and other hematophagous arthropods, the primary vectors of multiple parasites and viruses, are responsible for the transmission of serious diseases to humans. Nowadays, the interest is focused on the development of novel repellents to the existing ones with advanced properties. The present study attempts the discovery of novel hit compounds which may evolve as insect repellents using a combined computational methodology targeting the Odorant Binding Protein 1 (OBP1). The in silico results indicated two compounds, namely coniferyl alcohol and 1,2‐diphenyl‐2‐propanol, which were further evaluated (a) in vitro for their binding affinity to AgamOBP1 and (b) in vivo using dose‐dependent repellence tests against the aggressive‐day biting Aedes albopictus. The combination of in vitro and in vivo results pointed that coniferyl alcohol and 1,2‐diphenyl‐2‐propanol exhibited high binding affinity over OBP1 with 69.4 and 84.7 nM, respectively as well as efficient repellent activity. Compounds were also tested for their dose‐dependent repellency activity in vivo against Aedes albopictus. Overall, the selected compounds can serve as scaffolds for the development of novel repellents. An ounce of prevention: The current study aims to contribute toward the discovery of improved insect repellents. For this scope, a combined virtual screening methodology, including in silico techniques, was performed to identify potential hits. The results indicated five compounds with insect repellent activity in comparison with untreated hand. All selected compounds can be exploited for further hit to lead optimization process.