Background and objectives: A considerable increase in the levels of adenoviral diseases among both adults and children necessitate the development of effective methods for its prevention and treatment. The synthesis of the new fluorinated 1,2,3-triazoles, and the study of the mechanisms of their action, are promising for the development of efficient antiviral drugs of our time. Materials and Methods: Antiviral activity and cell cytotoxic effect of 2-(3-chlorotetrahydrofuran-2-yl)-4-tosyl-5-(perfluoropropyl)-1,2,3-triazole (G29) were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The influence of the compound on the infectivity of human adenovirus type 5 (HAdV-5) was carried out via the cytomorphology method. The influence of the compound on the cell cycle under a condition of adenovirus infection was studied using flow cytometric analysis of propidium iodide-stained cells. Results: It was found that G29 suppressed HAdV-5 reproduction by 50% in concentrations of 37 μg/mL. Furthermore, the compound reduced the titer of virus obtained de novo, and inhibited HAdV-5 inclusion bodies formation by 84–90%. The use of fluorinated compounds under the conditions of adenovirus infection decreased the number of apoptotic cells by 11% and the number of cells in S phase by 21–42% compared to the profile of infected cells. Conclusions: The fluorinated compound G29 showed moderate activity against HAdV-5 based on several mechanisms. It led to the normalization of the life cycle of cells infected with adenovirus to the level of non-infected cells and caused the obstruction of HAdV-5 reproduction, inducing the formation of non-infectious virus progeny.
The aim of the study: to investigate the peculiarities of the development of the pathological process in cells in conditions of mixed viral infection and to study the effectiveness of antiviral drugs in this model. Materials and methods of research. A model of simultaneous mixed infection of MDBK cells with human adenovirus serotype 5 (HAdV-5) and herpes simplex virus type 1 (HSV-1) was developed. Mitochondrial activity, ultrastructure and the state of the cell population were studied using MTT assay, transmission electron microscopy and flow cytometry with propidium iodide dye. The intensity of virus reproduction in cells and their infectious titer were studied by the cytomorphology method. The level of the synthesis of the major proteins of associate viruses was analyzed using flow cytometry and the corresponding monoclonal antibodies. Results of the research. Co-infected cells demonstrated a lower rate of development of pathomorphological changes compared to mono-infections, related to the inhibition of the reproduction of associate viruses. It was found that the co-infection of cells with HSV-1 and HAdV-5 results in a decrease in the number of cells with virus-induced intranuclear inclusions of both viruses by up to 40 % and viruses titer by 1.6 lg and 2.6 lg, respectively. Inhibition of synthesis of major capsid protein and glycoproteins of the herpes virus by 83 % and 64 %, respectively, and a less pronounced decrease in the amount of adenovirus hexon protein (by 17 %) were also noted. It is shown that the mitochondrial activity of co-infected cells increases to 64 % in comparison with herpetic mono-infection. An analysis of the influence of co-infection on cell cycle revealed that the number of cells in G1 phase remained unchanged compared with both mono-infections, while the number of apoptotic cells compared with herpes infection was reduced by 24 %. An analysis of the officinal drugs Acyclovir and Ribavirin effectiveness in conditions of mixed infection showed a reduction in their antiviral activity against associate viruses by 1 to 2.3 lg compared to mono-infections. Conclusions. The presence of a specific innovative cellular model of mixed infection with known aspects of the course of associated infections allows it to be used for preclinical study of antiviral activity of compounds and to obtain new data of the role of viral-viral interactions in the development of inefficient application of antiviral agents in medical practice. Key words: mixed viral infection, cytomorphological changes, cell cycle, reproduction of associate viruses, and antiviral activity. For citation: Biliavska LO, Povnitsa OY, Pankivska YB, Zagorodnya SD. Development of pathological process and activity of etiotropic drugs in cell culture under condition of viral co-infection. Journal of the National Academy of Medical Sciences of Ukraine. 2019;25(4):476–87
Over the past 10 years, many scientific groups have experimentally shown that non-functionalized nanoparticles show a pronounced antiviral and antimicrobial action against different pathogens. In order to understand the mechanism of nanoparticles action it is important to know its peculiarities, i.e. dependences on different nanoparticles and pathogen properties.In this work we studied how Au nanoparticles act on the viruses outside and inside the cell, and compare this action for two sizes of nanoparticles and two types of the viruses. The study has been conducted for adenovirus and H1N1 influenza virus, and nanoparticles of 5 nm and 20 nm diameter.Virucidal and antiviral actions were observed experimentally for both types of nanoparticles against both viruses. It has been shown that intensity of virucidal action depends on the nanoparticles concentration non-monotonically for adenovirus. It has also been shown with electron microscopy that the viruses are destructed after 5 nm nanoparticles adsorption on their surface; and that the viruses change their shape after 20 nm nanoparticles adsorption on their surface. The model of physical adsorption of nanoparticles on the virus surface due to near-field interaction proposed in previous works may explain observed results on virucidal action of nanoparticles.
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