Molecular Dynamics Simulation for Rabies Antiviral Treatment

• Grant number: 22/07128-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2023
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Principal Investigator: Paulo Eduardo Brandão
• Grantee: Joana Rocha da Silveira Barreto de Aguiar
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rabies is a zoonotic disease that mainly affects poor populations in developing countries. While there is an efficient vaccine against rabies, many of those in the areas most affected by the disease are not aware of the vaccination requirements and may be unable to reach an area where vaccines are readily available, or unable to pay for vaccination and immunoglobulin. This project aims to find a potential treatment for the disease when it has already reached its later stages, so those who can't access vaccination still have a chance of surviving. Following a Master's project that focused on molecular docking to find potential ligands that could work against the rabies virus (RABV), this project will work with another bioinformatic tool (molecular dynamics) to narrow down the field of potential ligands even further. Molecular dynamics will be used to check how each of the five proteins of RABV interact with ligands that have shown potential in inhibiting the proteins through binding in molecular docking. In contrast with molecular docking, molecular dynamics goes one step further in this search for treatment, checking for protein-ligand interactions in a setting that more closely resembles a cell, as it allows the user to add waters to the system, and use different conditions of temperature, pressure, and pH. Upon completion of molecular dynamics, in vitro assays will be conducted using N2A cells to further check if these ligands can inhibit the proteins of RABV.