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

Abstract

The Chikungunya virus (CHIKV), which causes Chikungunya fever, is an arbovirus transmitted by the Aedes aegypti mosquito, which periodically causes epidemics around the world. Since the 2014 outbreak in Brazil, the number of cases of CHIKV infection has increased and could become a serious public health problem. A viral infection causes several symptoms, which can result in arthritis and neurological disorders. However, there are no vaccines or drugs against CHIKV that can mitigate the spread of the virus and limit the morbidity associated with the disease. The quick and efficient identification of antiviral agents depends on cellular / biochemical assays that can be performed in high throughput screening format (HTS), such as replicon-based assays. These are subgenomic systems in which the genes encoding the viral proteins are replaced by a reporter protein, which allows the identification of inhibitors of viral replication in a safe way, once transfected in susceptible cells. In this project, we will use a CHIKV reporter lineage replicon, called BHK-21-Rep-T7-Gluc-nSP-CHIKV-99650, for screening large libraries of small molecules in HTS format. The cells express the subgenomic replicon of the virus containing the Gaussia luciferase (Gluc) gene as a reporter and of the neomycin phosphotransferase (Neo), to maintain this system stably in the cytoplasm. This project is linked to CEPID CIBFar from FAPESP and aims to identify potential anti-CHIKV agents, contributing to the development of drugs against emerging arboviruses.