Development of a Novel Aedes aegypti Repellent: An Integrated Approach Combining In Silico and Bioassays

Area of Science:

• Entomology
• Toxicology
• Computational Chemistry

Background:

• Aedes aegypti mosquitoes transmit arboviruses, causing widespread disease.
• Odorant-binding protein 1 (AaegOBP1) in A. aegypti is crucial for host-seeking behavior and is a potential target for repellents.

Purpose of the Study:

• To identify and prioritize potential repellents targeting AaegOBP1.
• To evaluate the efficacy of ZINC71773878 as a repellent against A. aegypti.

Main Methods:

• In silico screening and validation using molecular dynamics.
• Bioassays to assess repellency rates at various concentrations.
• Constant pH molecular dynamics (CpHMD) to study complex dissociation.

Main Results:

• ZINC71773878 demonstrated a dose-dependent repellency.
• At 3000 µmol/100 µL, ZINC71773878 exhibited higher repellency than DEET.
• CpHMD elucidated pH-dependent interactions between AaegOBP1 and ZINC71773878.

Conclusions:

• ZINC71773878 is a promising candidate for developing advanced mosquito repellents.
• Further trials are recommended to develop safer and more effective repellents than current options in Brazil.