Porva J. The modelling of hepatitis virus C infection in vitro and the investigation of antiviral activity of drugs belonging to flavonoids and elagotannins group

Dissertation is devoted to the development of effective methods of hepatitis virus С (HCV) cultivation, creation of hepatitis virus C experimental model in vitro and investigation of antiviral activity of drugs belonging to flavonoids and elagotannins groups. Optimal methods for HCV cultivation in vitro were modified; comparative analysis of sensitivity of different cell cultures was performed. It was determined that cultures of cell lines NGUK and ОН-1 appeared more effective for HCV replication in vitro. It was shown that modified isolation technology of cultivation with the use of tripsin treatment is more effective since the increased rate of infected cell cultures with reproduction of HCV was observed. Productive cultures of cells МТ-4 were obtained and transfected with HCV cDNA that was created from RNA purified from blood of hepatitis C patients. These cell cultures showed stable production of HCV before and after cryopreservation of transfected MT-4 cells. The modelling of the infection of bovine viral diarrhea virus (BVDV) was demonstrated. This virus represents a typical surrogate model of HCV for the investigation of antiviral drugs effects because of its reproduction in vitro in cell culture and has similar structural genes as HCV. The results of work showed antiviral activity against HCV of drugs belonging to flavonoids (Proteflazid) and elagotannins (Altabor) under preventive and treatment scheme and simultaneous injection of both medicines.