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1.
Medicina (Kaunas) ; 55(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443536

RESUMO

Background and objectives: The use of antagonistic probiotic microorganisms and their byproducts represents a promising approach for the treatment of viral diseases. In the current work, the effect of exopolysaccharides (EPSs) produced by lactic acid bacteria from different genera on the structural and functional characteristics of cells and the development of adenoviral infection in vitro was studied. Materials and Methods: Cytotoxicity of six EPSs of lactic acid bacteria of the genera Lactobacillus, Leuconostoc and Pediococcus was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The influence of the EPSs on the infectivity of human adenovirus type 5 (HAdV-5) and on the cell cycle under a condition of adenovirus infection was studied using plaque reduction assay and flow cytometric analysis, respectively. Results: It was shown that exopolysaccharides were non-toxic to Madin-Darby bovine kidney cells (MDBK) as they reduced their viability by 3-17%. A change in the distribution of the cell cycle phases in the non-infected cell population treated with EPSs was observed. The analysis demonstrated an increase in the number of cells in the S phase by 47% when using EPSs 15a and a decrease in the number of cells in the G1 phase by 20-27% when treated with the EPSs 15a, 33a, and 19s. The use of EPSs did not led to the normalization of the life cycle of HAdV-5 infected cells to the level of non-infected cells. The EPSs showed low virucidal activity and reduced the HAdV-5 infectivity to 85%. Among the studied exopolysaccharides, anti-adenovirus activity was found for EPS 26a that is produced by Lactobacillus spp. strain. The treatment of cells with the EPS following virus adsorption completely (100%) suppressed the formation and release of HAdV-5 infectious. Conclusions: EPS 26a possessed distinct anti-HAdV-5 activity and the obtained data demonstrate the potential of using exopolysaccharides as anti-adenoviral agents.


Assuntos
Adenovírus Humanos/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Lactobacillus/metabolismo , Leuconostoc/metabolismo , Pediococcus/metabolismo , Polissacarídeos Bacterianos/farmacologia , Infecções por Adenovirus Humanos/prevenção & controle , Animais , Linhagem Celular , Cães , Fase G1 , Humanos , Lactobacillales/metabolismo , Polissacarídeos Bacterianos/metabolismo , Fase S
2.
Medicina (Kaunas) ; 54(5)2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30400656

RESUMO

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.


Assuntos
Adenovírus Humanos/efeitos dos fármacos , Antivirais/síntese química , Antivirais/farmacologia , Compostos de Flúor/síntese química , Compostos de Flúor/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Infecções por Adenovirus Humanos/tratamento farmacológico , Infecções por Adenovirus Humanos/prevenção & controle , Animais , Antivirais/química , Antivirais/uso terapêutico , Caseína Quinase II/antagonistas & inibidores , Bovinos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Compostos de Flúor/química , Compostos de Flúor/uso terapêutico , Microscopia de Fluorescência , Mimetismo Molecular , Triazóis/química , Triazóis/uso terapêutico , Replicação Viral/efeitos dos fármacos
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