Seleção de peptídeos reativos aos soros de pacientes HCV+ e sua influência no desenvolvimento da fibrose hepática

Abstract

Hepatitis C is a public health problem that affects more than 185 million people worldwide. It is a disease with very variable prognosis that can progress to cure or to the development of chronic hepatitis C, liver cirrhosis, hepatocellular carcinoma and death. Despite the high sensitivity and specificity of screening methods for the hepatitis C virus, there is a great need to reject markers that are capable of predicting disease chronicity, with acceptable percentages of sensitivity and specificity. The identification of new surface epitopes and their mimotopes is of great value for the development of nanotechnology platforms that can be used as new rapid and specific diagnostic strategies for this and other pathologies in populations at risk. Phage Display technology has been proposed as one of the promising tools to develop new diagnostic tests due to its ability to interact with biomolecules, in addition to being able to generate products that meet the requirements of clinical laboratories in a cost-effective way. This proposal aimed to: a) select mimetic peptides to HCV antigens reactive against total purified IgG from patients with different stages of liver disease; b) verify the reactivity of the clones obtained against IgG in pooled sera from patients with severe hepatic fibrosis; c) compare the similarity of peptides found with other Hepatitis C virus proteins in a silica analysis. Through the biofilling process, 83 incomplete clones reactive to patients with Severe Fibrosis were selected. Of these, 6 clones were related to an F protein, one potentially involved in the chronicity of hepatitis C. After performing the in-silico analysis, a mimetopes of a possible epitope of the HCV F protein that may be interacting with the glutathione S-enzyme was identified. transferase A3 (GSTA3), known to inhibit the fibrogenic process in liver stellate cells. With the development of the project, it was found that mimetic peptides reactive to sera from HCV patients selected by the Phage Display technique seems to be promising for use in diagnostic assays in liver fibrosis.