Assessment of synthetic peptides on directed Hepatitis C Virus inhibition

• Grant number: 16/02174-4
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2016
• Effective date (End): July 31, 2018
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Paula Rahal
• Grantee: Mariana Nogueira Batista
• 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
• Associated scholarship(s): 17/00287-9 - Adaptation of a rat derived HCV-RELATED rodent Hepacivirus to the mouse host, BE.EP.DR

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BATISTA, MARIANA NOGUEIRA; DA SILVA SANCHES, PAULO RICARDO; CARNEIRO, BRUNO MOREIRA; SILVA BRAGA, ANA CLAUDIA; FERNANDES CAMPOS, GUILHERME RODRIGUES; CHILLI, EDUARDO MAFFUD; RAHAL, PAULA. GA-Hecate antiviral properties on HCV whole cycle represent a new antiviral class and open the door for the development of broad spectrum antivirals. SCIENTIFIC REPORTS, v. 8, SEP 25 2018. Web of Science Citations: 0.