Assessment of synthetic peptides on directed Hepatitis C virus inhibition

Abstract

Hepatitis C is the liver inflammation arising from hepatitis C virus (HCV) infection, frequently it evolves to chronic conditions and has been considered worldwide the major cause of cirrhosis and hepatocellular carcinoma, reported as the main world public health problem. It is estimated that 150 million of people have chronic infection by this vírus and that 3 to 4 million of new cases arise each year. The main HCV transmission pathway is parenteral and current treatments are based on PEG-IFN and ribavirin along with second generation direct acting antivirals. The last ones presents much side-effects, high costs and resistant mutants has been reported. Therefore, new effective treatments, less expensive, with higher spectrum and lower side-effects have been sought. Thus, the aim of this study is to develop a prodrug with directed action for HCV infected cells and efficient against more than one step of viral replication cycle For that, an initial screening will be performed for five synthetic peptides subsequently modeled for prodrugs production, what will be analized using the viral replication models J6/JFH-1 RLUC e JFH-1, the subgenomic replicons SGR-JFH1-Feo (genotype 2) e S52/SG (genotype 3); and the cell line Huh-7.5. The analysis will include citoxicity assay, luciferase-based assay and western blotting for inhibitory capacity of compound on viral replication; indirect immunofluorescence for entry assays and qPCR for compounds effect on viral release step assessment.