STUDY OF INCLUSION BODIES MODULATING DRUGS AS ANTIVIRALS AGAINST RABIES

• Grant number: 24/03029-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Paulo Eduardo Brandão
• Grantee: Mariana Vespar Teixeira
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rabies is a zoonosis capable of affecting wild and domestic animals. It is widely distributed throughout the world and culminates in infection of the central nervous system, evolving in an acute, gradual and fatal manner. In the preventive and therapeutic scenario, there are measures such as vaccination, immunotherapies and palliative actions, but without antiviral effectiveness to delay the infection installed at the nervous level. The rabies virus (RABV) has genetic material composed of a linear strand of simple RNA with negative polarity which, during the infection process, induces the rearrangement of the host cell's cytoskeleton, culminating in the formation of cytoplasmic inclusion bodies, known as Negri bodies when found in infected nerve cells. Evidence shows that these formations, thus consolidated, can act as a site composed of essential elements for the occurrence of viral replication, which allows them to be promising targets for the development of antivirals. Moreover, curcumin has already been shown to be effective in hardening the inclusion bodies, while lovastatin, by interfering with cholesterol metabolism, has caused instability and increased fluidity, both leading to a decrease in viral replication. Finally, the present work is a study to evaluate the impact of RABV replication in antiviral assays with different doses of curcumin and lovastatin in cell culture in microplates by means of immunofluorescence analysis and real-time PCR. The data obtained from this study can help the development of new antivirals, which could help veterinary and human medicine in the fight against rabies.