Discovery of compounds with antiviral activity against the Chikungunya virus (CHIKV) nsP2 protease

Abstract

The Chinkunguya virus (CHIKV) is an arbovirus from the Togaviridae family, transmitted by the bite of mosquitoes of the genus Aedes. Infections caused by CHIKV were first recorded in Tanzania in 1952, and in the last decade the virus has spread to more than 100 countries in the Americas, Africa, Europe and Asia, including Brazil, where the number of cases has been increasing since the first outbreak in 2014. To date, there is no antiviral and no vaccine available, making the need for specific treatment against CHIKV increasingly urgent. The virus's nsP2pro, a cysteine protease, is responsible for processing the nsP1234 polyprotein into the four individual non-structural proteins (nsPs) (nsP1 to 4), which form the viral replication complex, thus being a promising target for drug development. . Thus, the objective of the present work, which is linked to the CEPID CIBFar of FAPESP (Process 2013/07600-3), is to obtain in a recombinant form and characterize the CHIKV protease and use it as a target in biochemical assay to identify compounds of the GHP Box library (MMV/DNDi) with anti-CHIKV action. The activity of the selected compounds will be validated through phenotypic assays using the CHIKV replicon reporter strain, BHK-21-RepT7-Gluc-nSP-CHIKV-99650, to determine the efficacy and toxicity of these molecules.