Research on compounds with potential antiviral action for Mayaro and Oropouche viruses

Author(s)

Aline Lavado Tolardo

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-01-13

Examining board members

Luiz Tadeu Moraes Figueiredo; Gustavo Olszanski Acrani; Rodrigo de Carvalho Santana; Ricardo Luiz Moro de Sousa

• Advisor: Luiz Tadeu Moraes Figueiredo

Abstract

Alphavirus and Orthobunyavirus are important arboviruses that have a major economic and social impact in Brazil. There are no antivirals available to treat these viruses. Therefore, it is essential to have therapeutic drugs that combat the symptoms and signs manifested by the disease in mild and moderate cases. In this thesis, we developed a cell-based luminescence assay for the screening of potential small molecules for Mayaro and Oropouche viruses that measures the virus-induced cytopathic effect (CPE) in Vero cells (ATCC CCL81) using the luminescence-based CellTiter Glo system. The assay was validated in a 384-well plate format and showed Z values greater than 0.7, background greater than 30 and signal-to-noise greater than 10, demonstrating high capacity. Four compound libraries were tested at a concentration of 10 µM for both tests. We identified five compounds that inhibited virus-induced cytopathic effect by> 50%, with EC50/CC50 values comparable to those determined by other cell-based assays, thus validating the assay\'s accuracy and ability to serve as a tool for discovery of new antivirals for Mayaro and Oropouche viruses. (AU)

• FAPESP's process: 16/17457-1 - Compounds screening with potential antiviral action against Alphaviruses and Orthobunyaviruses
• Grantee: Aline Lavado Tolardo
• Support Opportunities: Scholarships in Brazil - Doctorate