الفهرس | Only 14 pages are availabe for public view |
Abstract Hepatitis C virus (HCV) is a leading cause for chronic liver diseases and it was already recorded that at least 170 million people worldwide are HCV infected. It accounts for 20 to 30% of cases of acute hepatitis. To date at least six major genotypes are recognized, each having multiple subtypes, have been identified worldwide. The different genotypes are relevant to epidemiology, vaccine development, and clinical management of chronic HCV infection. HCV genotype 4 is mostly predominant in Egypt. At the moment the only accepted antiviral therapy with proven effectiveness is a combination of PEG-ylated Interferon α and Ribavirin The present work was aiming to evaluate the efficency of 3 current available antiviral drugs either they derived biotechnology (IFN) or synthetically (Ribavirin and DDB). The present work also gave a highlight on the maximum bioavilability of such drugs when they applied singly or mixed togather for synergetic promotion activity. Since the mode of action of antiviral drugs was vary among them. It was well establised that the mechanism of action of IFN act on the synthesis of MX protein production developed post expression of MX gene as a biomarker that initiates MX protein production. This protein interferes (inhibit) the replication cycle of viruses. MX gene was detected in the human and animal tissues as Mxa and MXb. In this study, two cell lines namely African green monkey cells (Vero) and Human hepatoma cells (HepG2 cells) were maintained , splitted and preserved in cell bank of target cell lines according to established protocols. Seed stock of Vesicular Stomatitis virus (model virus was used instead of HCV) seed stock was prepared in Vero cells then virus infectivity titer end point was determined 107.68 TCCD50. The results of this study can be summarized in the following: 1- Cytotoxicity of Interferon alpha-2a, Ribavirin and DDB was carried out on Vero and HepG2 cell lines. Evaluation of residual living cells was arranged using MTT assay. The results revealed that Interferon was completely safe to both cell lines at any appplied concentration where no toxicity was detected. While toxicity of Ribavirin to Vero and HepG2 cell lines showed a residual viability in the order of 60% and 58% when used at 1200 μg/ml. While, the concentration of 300μg/ml showed 100 % safety for both cell lines either treated with Ribavirin or DDB. 2- Evaluation of antiviral activity under the effect of antiviral drugs on both cell lines revealed that the reactivity of Vero cells to antiviral drugs was somewhat better than that of HepG2 cells. A better pattern to antiviral activity for both Interferon and Ribavirin while a less effective role to DDB as antiviral was detected in Vero cell line. The least effect on viral infectivity titer was detected on HepG2 cell lines by using DDB. |