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Evaluation of synthetic peptides on Chikungunya Virus inhibition

Grant number: 19/10150-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2019
Effective date (End): February 28, 2023
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Paula Rahal
Grantee:Gabriela Miranda Ayusso
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Arboviruses are diseases caused by a group of virus (arbovirus) which has hematophagous arthropods as transmission vectors. These diseases present high economic and social impact, representing a serious public health problem. Chikungunya virus (CHIKV) is an arbovirus which belongs to the family Togaviridae and is grouped within the genus Alphavirus. To date, no licensed anti-CHIKV therapy or vaccine is available and only palliative cares are recommended to relieve symptoms. Although the mortality rate is modest, the debilitating and chronic nature and economic burden associated with CHIKV infection demonstrate the significant need for safe, effective and economical treatments or vaccines to reduce viral spread and limit disease burden. Peptides and gallic acid (GA) present wide biological activity, highlighting the antiviral. Recently, our group described the anti-HCV activity of a GA-conjugated peptide which, in addition to demonstrate low cytotoxicity, promoted significant viral inhibition at major steps of HCV replication cycle. In the present project, the toxicity of eight GA-conjugated antiviral peptides will be determined in newborn hamster kidney fibroblasts cells (BHK-21) and human hepatoma cells (Huh-7) by MTT (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. Peptides which demonstrate percentage of cell viability greater than 80% will have their antiviral activity evaluated over the complete replication cycle of CHIKV. Peptides which exhibit activity against CHIKV will be investigated regarding the inhibition effect on steps of viral entry (adsorption and internalization) and release. Additionally, peptides will also be analyzed regarding the inhibitory effect on viral infectivity and in relation to direct inactivation capacity of extracellular viral particles. In all assays, the anti-CHIKV activity will be measured by quantification of viral RNA.