ANALYSIS OF THE RECOMBINANT NON-STRUCTURAL PROTEINS OF WEST NILE VIRUS (WNV)

• Grant number: 25/14277-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2025
• End date: August 31, 2029
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Edison Luiz Durigon
• Grantee: Bruna Campestrini Casarin
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/07746-0 - Drug discovery against human viral infectious diseases, AP.TEM

Abstract

The West Nile Virus (WNV), a mosquito-borne flavivirus, has shown a growing global incidence, with the potential to cause neuroinvasive diseases in humans. Currently, only palliative treatments are available, highlighting the urgent need for new therapeutic approaches. Thus, the objective of this project is to assess compounds that can inhibit the activity of WNV NS3 and NS5 proteins, seeking to identify new antiviral targets. Constructs of the viral NS3 and NS5 proteins, optimized for expression in Escherichia coli, will be synthesized. Following expression and purification, the enzymatic activity of both proteins will be determined using colorimetric and RNA capping assays, respectively. The evaluation of NS3 and NS5 as therapeutic targets will be conducted through protein-protein interaction assays via ELISA or isothermal titration calorimetry (ITC). Promising compounds will be tested for protein-compound interaction using specific equipment or by co-crystallization, aiming to determine the crystallographic structures of the complexes. (AU)