Searching for peptide ligands for proteases from Zika, Yellow Fever, Chikungunya and Mayaro arboviruses using Phage Display

• Grant number: 23/04491-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2024
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Paula Rahal
• Grantee: Dayla Bott Geraldini
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated research grant: 20/08615-8 - Protein exosites, cryptic sites and moonlighting: identification, functional mapping and effects of changes in structure, AP.TEM

Abstract

Arboviruses are viruses transmitted by hematophagous arthropods (mosquitoes and ticks), and are kept circulating in urban and wild cycles, and currently represent a public health problem in several countries. The emergence and reemergence of arboviruses are natural phenomena related to the evolution and adaptation of these viruses. Brazil, having large areas covered by tropical forests, has ideal conditions for the occurrence and maintenance of the sylvatic cycle of several arboviruses. The increasing urbanization, the migratory flow, the destruction of natural habitats and the presence of mosquitoes of the Culex and Aedes genera favor the rapid dissemination of these viruses. In Brazil, the main arboviruses that cause epidemics belong to the Flaviridae (DENV, ZIKV, YFV) and Togaviridae (CHIKV, MAYV) families. Such viruses are responsible for diseases present in Brazil, which emphasizes the importance of research and continuous study on these viruses that have genomic organization and replication strategy in common that is based on dependence on a viral protease responsible for processing its polyprotein into functional components. Although the mechanisms of action of these enzymes are widely known, little is known about the modulating role of partner proteins that specifically interact with their exosites. There are still no vaccines in the public network or any other preventive medicine against most arboviruses, except for Yellow Fever, which still has low vaccination coverage in society. Recently, the development of peptide drugs has received a lot of attention because of their greater safety and lower cost of development. Phage Display is a technique based on the expression of peptides on phage capsids, used for the purpose of selecting specific protein ligands from genomic libraries. In recent years, this technology has allowed the rapid screening of functional peptides and has proven to be valuable both for drug development and for identifying ligands with the potential to inhibit and enhance enzymatic activities. for use in identifying peptide molecules for pharmaceutical development. Therefore, the objective of this project seeks to identify peptides with antiviral potential against Zika, Yellow Fever, Chikungunya and Mayaro arboviruses using the Phage Display methodology. These data will be used as a basis for other members of the FAPESP 2020/08615-8 thematic project team to carry out structural studies in order to understand the binding modes between peptides and protein targets.