Screening of compounds for the identification of drugs against the Zika virus using a subgenomic replicon system

• Grant number: 21/01686-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2021
• Effective date (End): October 31, 2022
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Glaucius Oliva
• Grantee: Isabela Dolci
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

The Zika virus is an arbovirus transmitted by the bite of the Aedes aegypti mosquito, which became a public health problem during the 2015/2016 outbreak in the Americas and mainly in Brazil, where it was related to cases of microcephaly and Guillan-Barré syndrome. The identification of autochthonous cases in 87 countries in 2019, shows ZIKV's enormous potential to emerge in the future as a new epidemic. Therefore, the search for effective drugs against viral infection is necessary, since there are still no vaccines or drugs available against ZIKV. The identification of antiviral agents quickly and efficient depends on cellular/ biochemical assays that can be performed in high throughput screening (HTS), such as replicon-based assays. These are subgenomic systems, in which the genes that encode the structural proteins are replaced by a reporter protein, which allows the identification of viral replication inhibitors in a safe way, once transfected in susceptible mammalian cells. In this project, we will use the ZIKV replicon reporter cell line, named BHK-21-RepZIKV_IRES_Neo, recently developed by our research group, for the screening of large libraries of small molecules in HTS format. These cells express the viral replicon containing the Renilla luciferase gene and the neomycin phosphotransferase gene, which allows the maintenance of this system in a stable manner in the cytoplasm. This project is linked to CEPID CIBFar of FAPESP and aims to identify potential anti-ZIKV agents, contributing to the development of drugs against emerging arboviruses.