SELECTION OF COMPOUNDS THROUGH DRUG REPURPOSING AND CHARACTERIZATION OF ANTIVIRAL ACTIVITY AGAINST OROPOUCHE ORTHOBUNYAVIRUS

• Grant number: 22/02278-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Rafael Elias Marques Pereira Silva
• Grantee: Alexandre Borin Pereira
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated scholarship(s): 23/16611-0 - Study of immune innate cell migration in a zebrafish model infected with Orthobunyavirus oropoucheense, BE.EP.DR

Abstract

Oropouche orthobunyavirus (OROV) is the causative agent of Oropouche Fever, a disease spread mainly in the Amazon region and Central America. Like other arboviruses, the disease evokes symptoms of fever, myalgia, body aches and headaches. OROV has affected more than half a million people in the last 50 years in Brazil. Despite this, there is no vaccine or specific treatment for the disease. Therefore, the use of the drug repurposing strategy in order to find a treatment for Oropouche Fever appears to be a quick and inexpensive alternative for the identification of possible candidates for the treatment of this neglected disease. Drug repurposing has already been used by industry to find new uses for compounds such as sildenafil and was widely used during the COVID-19 pandemic with the FDA approval of remdesivir.As preliminary results, we established a stock of OROV in our laboratory, and determined the time-points for antiviral assays between 24h and 48h post infection in Vero cells. We have standardized Multiplicities of Infection (MOI) for infection and antiviral testing. Also, and we have already performed preliminary assays for the selection of repurposed compounds with cytoprotective activity in Vero cells. With our results, we started preliminary assays to validate the antiviral activity of 6 compounds. Furthermore, we started the padronization of OROV infection in Ifnar-/- immunodeficient mice to perform drug testing. Moreover, we performed an pilot experiment to establish a lethality curve in relation to viral load and survival time. In conclusion, this doctoral project aims to select compounds with antiviral activity against OROV using different cell lines and validate the results in an in vivo model.