The article contains results of a study of cytotoxicity and antiviral effect of investigated drugs against RNA-containing viruses of fish. Search for and development of means of application of new safe and effective drugs, which have an immunomodulating effect on fish, is one current trends of fisheries science. Following drugs have been used in this work: Proteflazid – a drug developed by the SPC “Ecofarm” Ukraine, Kyiv. The drug contains: sums of carboxylic acids as equivalent to apple acid – 6. 3 g, flavonoids as equivalent to rutin – 0. 32 g (flavonoid glycosides extracted from wild cereals Deschampsia caespitosa L. and Calamagrostis epigeios L.). Flavonoid glycosides contained in wild cereals Deschampsiacaespitosa L. та Calamagrostis epigeios L. are able to inhibit virus-specific enzymes DNA- polymerase and thymidine kinase in virus-infected cells. We used a drug concentrate, 20 ml of which were dissolved in 4 ml of Eagle’s medium DMEM. Groprynozyn (Inosine pranobex). Active drug substance is inosine pranobeks – molecular complex of inosine and 1 – (dimethyl amino) -2 – propanol-4 – atsetaminobenzoatu at a ratio of 1:3. The drug has antiviral and immunostimulatory activity Izatizon is a complex drug, which contains substances used as independent medicinal products in medical practice, namely Metisazon (Marboran), Dimethylsulfoxide (Dimexid), and Polyethylene glycol with a molecular weight of 400. During the work we used the drug Izatizon manufactured in conditions of the laboratory of the Institute of Molecular Biology and Genetics of the NAS of Ukraine. All above-mentioned drugs are widely used in human medicine for treatment of various viral infections. A possibility of their use in aquaculture attracts interest in scientists that can be an effective method for controlling viral infections, which are a cause of high death rate of fish. For determining antiviral effect, as a test object we selected Ukrainian isolates of infectious pancreatic necrosis virus (IPNV) VF-08 and isolate VCH-1 of spring viraemia of carp virus (SVC). Based on results of our previous studies, viruses of these systematic groups are the highest threat for freshwater aquaculture. For testing the drugs in conditions in vitro, we used a passaged EPC culture, which is optimal for SVC virus reproduction, and RTG-2 culture, which is optimal for IPN virus reproduction and accumulation. Results of determination of maximum acceptable concentrations (MAC) of the studied drugs in fish cell cultures are presented. It was found that at concentrations of Proteflazid – 19. 1 mcg/ml, Izatizon – 12. 5 mcg/ml, Groprinozid – 16 mcg/ml and lower concentrations, no degenerative changes of monolayer were observed in cell cultures in 96 hours and all cell lines preserved their ability for further cultivation. According to results of experimental studies, it was found that the proposed drugs have pronounced antiviral effects against spring viraemia of carp virus and infectious pancreatic necrosis virus and reduce the titer of infection viruses from 2 to lg ID50 in cultural systems. Based on economic considerations, for prevention and treatment of rhabdovirus infection of carp, it is advisable to use the drug Izatizon, while the drug Groprinozin can be used for brood fish. Application of these drugs should be performed in the context of developed complex measures and methods.
antiviral drugs, fish cell cultures, spring viraemia of carp virus, infectious pancreatic necrosis virus
«Bulletin of problems biology and medicine» Issue 1 (106), 2014 year, 61-65 pages, index UDK 578: 597. 2/. 5