Search for protease inhibitors with larvicidal activity for Aedes aegypti

• Grant number: 25/03924-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Aparecida Sadae Tanaka
• Grantee: Júlia Tiemi Sakata
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/03779-5 - Use of phage display as a tool in the diagnosis and control of diseases transmitted by hematophagous vectors, AP.TEM

Abstract

The Aedes aegypti mosquito is a hematophagous arthropod that is a vector of several arboviruses that affect humans, including Dengue, Yellow Fever, and Zika. In 2024, Brazil experienced a significant increase in the number of Dengue cases, and in 2025, the increase in the number of Yellow Fever cases has been a concern for health authorities. A vaccine against the Dengue virus was recently developed, but controlling the vector, the mosquito, remains an important strategic tool for combating arboviruses. Larvicides have emerged as a promising alternative for mosquito biocontrol, since they do not induce resistance in future strains of the vector, unlike what is observed with the continued use of chemical insecticides, one of the main forms of control today. In recent years, our group has conducted studies aimed at selecting specific inhibitors for digestive enzymes of Aedes aegypti larvae, aiming at their potential use as larvicides in vector population control. The results demonstrated that inhibitors that act on mosquito larval trypsin have the potential to interfere with insect development. Previous studies conducted by our group also resulted in the identification and characterization of trypsin (AAEL005607), the main digestive protease of Aedes aegypti larvae in the 4th instar stage. The objective of this study is to identify inhibitors of digestive trypsin in the 4th instar larvae of the mosquito Aedes aegypti and evaluate their potential larvicidal effect. To this end, the inhibitors will be expressed in a yeast system, purified by different chromatographic methods and finally, their inhibitory potential will be evaluated using a synthetic substrate. The inhibitors that show potential will be selected as candidates for future larvicidal trials.