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We studied the ability of the polyphenolic complex from Maackia amurensis, the active substance of Maksar, to inhibit the cytopathogenic effect induced by the SARS-CoV-2 and to reduce the concentration of viral RNA in infected Vero E6 cells. Polyphenolic complex showed significant anti-SARS-CoV-2 activity and effectively inhibited viral replication by direct action on viral particles and the early stage of viral infection.

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The quinoid pigment echinochrome A isolated from the sea urchin Scaphechinus mirabilis, the product of its oxidation dehydroechinochrome, and structurally similar antiviral agent oxolin were tested for their ability to inhibit plaque formation induced by herpes simplex virus type 1 (HSV-1) in Vero cells. The tested compounds showed significant anti-HSV-1 activity, mainly due to their direct effect on viral particles and on virus attachment to cells. The antiviral efficacy of the test compounds increased in the following order: oxolin→echinochrome A→dehydroechinochrome.

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Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors is cationic Cys-flanked peptides which form tight complexes with DNA due to electrostatic interactions and the presence of interpeptide disulfide bonds. The paper reports a comparative study of the physico-chemical, toxic, and transfectional properties of the DNA-peptide complexes obtained by matrix polymerization or oxidative polycondensation of Cys-flanked peptides using the chain growth terminator 2-amino ethanethiol. We have demonstrated the therapeutic effect of the delivery of the pPTK-1 plasmid carrying the herpes simplex virus type 1 (HSV-1) thymidine kinase gene into PANC-1, and HEK-293T cell culture as well as into primary UL cells. It has been shown that the carriers obtained by oxidative polycondensation transform primary UL cells more efficiently than those produced by matrix polymerization. Treatment with ganciclovir resulted in the death of up to 40% of UL cells transfected with the pPTK-1 plasmid. The perspectives of use of the polyR6 carrier produced by oxidative polycondensation as a tool for the development of modular peptide carriers for the purposes of UL gene therapy were discussed.

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Antiviral activity of the polyphenol complex from seagrass of the Zosteraceae family against highly pathogenic strain of the tick-borne encephalitis virus was studied on passaged culture of porcine embryo kidney cells. The antiviral effect of the test compound manifested in a decrease in the infectious titer of the virus and depended on the concentration and application schemes. Polyphenol complex in a concentration of 100 µg/ml suppressed accumulation of the pathogen in the cell culture: pretreatment of the virus reduced its titer by 4 log, pretreatment of cells by 1.4 log, and application of the compound 1 h after cell infection by 2.8 log. Antiviral action of the test compound is determined by direct inactivation of the virus and inhibition of virus replication at the early stage, which attests to potential of this compound in the treatment of tick-borne encephalitis.

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A possible approach to effective, pathogenetically valid treatment of patients with the tick-borne encephalitis (TBE) is a complex therapy with the immunotropic preparations isolated from natural objects. This work is devoted to the comparative study of the antiviral activity of the tinrostim (immunoactive peptide from the optical ganglia of the squid Berritiuthis magister) and some officinal drugs used for prevention and treatment of the TBE (ribavirin, reaferon-EC, cycloferon, 4-jodantipyrin, immunoglobulin human against encephalitis ixodicum) in the experimental models of the TBE. All tested drugs significantly inhibited the proliferation of the highly virulent strain of the TBEV in the sensitive PK cell cultures: ribavirin and immunoglobulin against TBE completely inhibited viral replication (by 100%); cycloferon - by 75%; tinrostim, reaferon-EC, and jodantipyrin - by 50-60%. Therapeutic efficacy of the compounds was evaluated on a model of acute lethal TBE in mice: treatment with cycloferon and immunoglobulin against TBE prevented the mortality in 35-45% of infected animals; tinrostim - in 25%; ribavirin, reaferon-EC, and jodantipyrin - in 5-10%. The combination of the immunoactive peptide, tinrostim, with officinal drugs (ribavirin, cycloferon) was more effective than the treatment with a single drug, thereby indicating the prospects of the use of this therapy for treating TBE.

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The review considers potential opportunities of certain antioxidants as antiviral agents for flavivirus infections. Currently flavivirus infections represent a significant public health problem for various regions of the world, since they result in high morbidity and mortality. Oxidative stress induced by viruses, including the flaviviruses, not only interferes with the body's important metabolic processes, but also regulates replication of the virus. A broad spectrum of antiviral activity of the natural phenolic antioxidants, i.e. rosmarinic acid and luteolin as components of the polyphenol complex isolated from the seagrass family Zsteraceae is decribed. The antiviral activity of rosmarinic acid and luteolin is shown to be due to their high antioxidant, antiinflammatory and neuroprotective potential. Particular attention is paid to the analysis of the activity of the polyphenol complex and its components against the tickborne encephalitis virus. The antiviral properties of the compounds with a broad spectrum of the biological action provide an oppor- tunity to consider them as promising candidates for combined therapy of tick-borne encephalitis.

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The results of macrophage metabolism studies at their infection by viruses differing in the level of virulence are presented. With the purpose of optimizing the estimation of viral cytopathogenic effects on macrophages, an index of cell reactions, which allows one to reveal the degree of virus influence in standard units, is offered. Generally, the application of high-sensitivity methods for functional activity determination and identification of the correlative communication between its changes and morphological features of cells can be prescribed to objective identification methods of not only viral reproduction, but also differentiation of types and the degree of their cytopathogenic effects.

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Tick-borne encephalitis virus infects neutrophils and induces their apoptosis, judging from moderate increase of succinate dehydrogenase activity and a trend to anaerobic energy production in neutrophils infected with the virus (shown by an increase of lactate dehydrogenase activity).

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Antiviral activity of 7,3'-disulfate luteolin, extracted from Zostera marina was studied on an experimental model of tick-borne encephalitis (TBE) in vivo and in vitro. The drug increased the survival of the experimental mice infected with TBE virus and prolonged their lifespan. It was shown that 7,3'-disulfate luteolin reduced the virus accumulation in the SPEV cells by 2.0-4.0 lg TCID50/ml.

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Oral use of Luromarin, extracted from sea algae Zostera asiatica, was efficient in protection of mice from lethal infection induced by highly pathogenic strain of TBE virus, by extending their average lifespan. Luromarin demonstrated potentiating action in combination with ribavirin and cycloferon.

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Luromarin, extracted from the sea alga Zostera asiatica, showed no cytotoxic activity when incubated with the SPEV cell culture and was characterized by virulicidal properties against highly pathogenic strain of TBE virus and the ability to inhibit the virus replication at the early stages of the infection.

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Stimulation of NO-producing activity of macrophages infected with tick-borne encephalitis virus was demonstrated. Activity of NADPH-diaphorase, inducible NO synthase, and cytochrome oxidase, a heme-containing mitochondrial enzyme reflecting NO production by the nitrite reductase pathway was observed against the background of production of NO metabolites by cells.

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Virological and morphological studies have established that tick-borne encephalitis (TBE) from virus-containing liquid is able to adhere to the surface of macrophages, to penetrate, and to multiple in them. Viral particles come into and out through local macrophageal plasmolemma lysis. The type of macrophageal infection is considered to be autonomic as genomic activation and TBE reproduction occurred in the cell cytoplasm. Productive acute lytic infection in the macrophages was due to the appearance of reproduction-induced adequate TBE with a pronounced cytopathic effect on cultured porcine embryo kidney cells and to the synthesis of virus-specific and virus-induced cytoplasmic organelles that caused cell deaths upon toxic and mechanical exposure.

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The authors have got an idea of the structure of the tick-borne encephalitis (TBE) virus population forming in the human body after tick bite in the south of the Far East. A hundred and forty-five antigen-positive samples were virologically studied in enzyme immunoassays. Human blood leukocytic virus isolation on the first day of tick suction testified to the capacity of the virus to adsorb and multiply just in the peripheral blood immunocompetent cells. The bulk (as high as 70%) of the TBE virus population was non-neuroinvasive strains, most of which could rapidly eliminate from man and albino mice. The neuroinvasive strains (as high as 30%) caused encephalitis in albino mice and different TBE forms (inapparent, feverish, focal). The sequences of 160 bp fragment of glycoprotein E gene of 24 strains have shown that they belong to one Far Eastern subtype of TVE virus.

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The metabolic activity of macrophages infected with tick-borne encephalitis virus (TBEV) affecting the human nervous system has been studied for the first time. The penetration and reproduction of TBEV in the macrophages stimulated their oxygen metabolism, increasing the activity of NADPH-oxidase complex, as well as the mitochondrial enzymes lactate dehydrogenase, succinate dehydrogenase, and cytochrome oxidase. A wave-like change in the activity of these enzymes in the macrophages reflected the reaction of the cells to the penetration of the virus in the first period (within 3 h) and to the synthesis of the virus particles and their exit into the extracellular space in the second period (from 5 to 48 h). In the macrophages infected with TBEV, accumulation of NO metabolites was observed. In the late period of the examination (1-4 days), the activities of superoxide dismutase and lysosomal enzymes (nonspecific esterase and acid phosphatase) were detected. Thus, the early increase in the activity of the cell enzymes indicates the activation of the macrophages, and the subsequent increase in their activity corresponds to the enhanced synthetic activity of the macrophages.

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Comparative investigation of immune status indices in patients with fever form of vernal encephalitis (group 1), with inapparent form with prolonged antigenemia (group III) and with short-term antigenemia (group II) was performed for the first time. Total 99 patients were under investigation. It was shown that in group I selective damage of immune system at T-level took place. In patients of group III immune system at all levels was less involved and humoral factor were changes. In patients in group II no significant change in immune system were registered. Activity of different immune correctors (thimalin, 4-iodoantipirine, leukinferon) was investigated in vitro. This preparations had stimulating effect in blood samples of patients with decreased immune status. In the patients with unchanged immune status no effect was demonstrated. The most prominent effect was revealed in the case of 4-iodoantipirine--interferon inducer.

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Suppressing effect of tick-borne encephalitis (TBE) virus on expression of lymphocyte subpopulation receptors has been demonstrated in vitro. Effects of 14 immunomodulators on expression of T lymphocyte receptors under the effect of TBE virus have been compared. Anti-TBE immunoglobulin, 4-iodantipyrin, and leukinferon had the highest protective effect after a preventive injection. Thymalin and leukinferon in combination with human leukocytic interferon were the most effective within the treatment protocols. Further studies of sensitivity of immunoregulator cells to immunomodulators is recommended with the aim of adding these drugs to therapy of TBE patients.

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