In vitro evaluation of peptides and bioconjugates against Chikungunya Virus (CHIKV) and utilization of murine model for assessing the efficacy and toxicity of hit compounds

• Grant number: 23/02956-6
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Paulo Ricardo da Silva Sanches
• Grantee: Paulo Ricardo da Silva Sanches
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Paula Rahal

Abstract

The Chikungunya virus (CHIKV) is among the arboviruses with the highest autochthonous circulation in Brazil, alongside other arboviruses like Dengue (DENV) and Zika virus (ZIKV). Globally, CHIKV epidemics have displayed a cyclical pattern characterized by remote outbreaks interspersed with periods of epidemiological silence, varying from years to decades. According to current surveys conducted by the World Health Organization, CHIKV has been reported worldwide, including in India, islands in the Indian Ocean, Southeast Asia, Europe, and the Americas. Its progression has been rapid and concerning, especially in regions with a hot and humid climate, conducive to the spread of vector insects. Infection leads to the sudden onset of symptoms in patients such as headaches, fever, muscle aches (myalgia), nausea, vomiting, and severe joint pain after an incubation period of 2 to 4 days.The use of animal models, primarily mice, in virus infection studies is widely employed because these animals exhibit similarities to humans, including genetic, physiological, and immunological resemblances. Furthermore, they are well-characterized laboratory animals with a wide range of available genetic manipulation tools, allowing for the creation of transgenic or knockout strains, thereby facilitating the study of viral infection processes.Thus, this project aims to evaluate the antiviral potential of synthetic peptides and bioconjugates in in vitro and in vivo tests to assess the efficacy and toxicity of these compounds against CHIKV. For in vitro assays, a complete virus construct based on the Chikungunya LR2006OPY1 isolate (East/Central/South African genotype) under a CMV promoter, containing the reporter gene for nanoluciferase (nLuc) in the Nsp3 protein region, will be used. The most promising compounds from the in vitro assays will have their efficacy and toxicity assessed in a murine model using AG129 knockout mice infected with the CHIKV-LR strain.This project is expected to identify promising compounds for the treatment of Chikungunya infections and provide crucial information regarding their efficacy and toxicity in a relevant animal model. (AU)