V V Zarubaev

Publications (20)5.34 Total impact

• Article: Morphogenesis of chronic lung lesions under the influence of proteolytic enzymes

  V. V. Zarubaev, V. P. Sukhinin
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  ABSTRACT: Acute and chronic pathological processes induced in murine lungs by influenza virus or intranasal administration of proteolytic enzymes chymotrypsin and proteinase K were compared. Histologic and electron microscopic analysis showed that a number of characteristics of these two processes were similar. These characteristics included serosanguineous lung edema on days 1–5 postinfection, infiltration of lung tissue with cell elements, metaplasia of bronchial epithelium, and presence of mycoplasma in chronic pneumonia foci. These parameters persisted during 150 days of the experiment without regression. The results suggest the key role of primary cell destruction and proteolytic activity enhancement in the development of chronic influenza-induced pneumonia.
  Bulletin of Experimental Biology and Medicine 04/2012; 128(1):760-763. · 0.27 Impact Factor
• Article: [Experimental study of Ingavirin antiviral activity against human adenovirus].

  V V Zarubaev, A V Slita, A K Sirotkin, V E Nebol'sin, O I Kiselev
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  ABSTRACT: Antiviral properties of Ingavirin were investigated in the Hep-2 cell culture with respect to the human respiratory tract virus (type 5 adenovirus). In concentrations of Ingavirin of 1000, 100 and 10 mcg/ml the generated posterity showed lower infective capacity (by 250, 100 and 10 times respectively). The electron microscopy of the infected cells confirmed the Ingavirin ability to disturb the adenovirus normal morphogenesis.
  Antibiotiki i khimioterapii͡a = Antibiotics and chemoterapy [sic] / Ministerstvo meditsinskoĭ i mikrobiologicheskoĭ promyshlennosti SSSR 01/2010; 55(9-10):19-24.
• Article: [Protective activity of Ingavirin in experimental lethal influenza due to pandemic influenza virus A (H1N1)v in albino mice].

  V V Zarubaev, A V Garshinina, N A Kalinina, A A Shtro, S V Beliaevskaia, V E Nebol'sin, O I Kiselev
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  ABSTRACT: Despite obvious success in the vaccine development and chemotherapy of influenza, it remains a poorly controlled infection leading to emergence of new pandemic variants of the virus with high morbidity and mortality. We investigated the protective activity of Ingavirin against the lethal influenza A (H1N1) 2009 virus infection on albino mice. Oral use of Ingavirin resulted in sharp decreasing of the mortality (index of protection up to 57%), slight decreasing of the infectious titer of the virus in the lungs (up to 40-fold), normalizing of the body weight dynamics and the lung tissue structure vs. the placebo-treated control. The degree of the bronchial epithelium damage was also strongly decreased. The results allow to consider Ingavirin as an effective antiviral against the current pandemic influenza virus.
  Antibiotiki i khimioterapii͡a = Antibiotics and chemoterapy [sic] / Ministerstvo meditsinskoĭ i mikrobiologicheskoĭ promyshlennosti SSSR 01/2010; 55(5-6):24-31.
• Article: [Experimental investigation of Ingavirin antiviral activity against human parainfluenza virus].

  V V Zarubaev, V Z Krivitskaia, V E Nebol'sin, O I Kiselev
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  ABSTRACT: The Ingavirin antiviral properties with respect to the parainfluenza virus, as an actual human respiratory tract pathogen, were investigated by two methods, i.e. immunoenzymatic analysis and microtetrazolium test. The results showed that along with the immediate antiviral activity Ingavirin had nonspecific cytoprotective properties. While affecting the virus proteins synthesis, Ingavirin lowered the virus cytopathogenic action. The drug significantly decreased the portion of the bronchial epithelium cells killed at the stage of acute infection.
  Antibiotiki i khimioterapii͡a = Antibiotics and chemoterapy [sic] / Ministerstvo meditsinskoĭ i mikrobiologicheskoĭ promyshlennosti SSSR 01/2010; 55(7-8):13-6.
• Article: Pristine Fullerene C60: Different Water Soluble Forms—Different Mechanisms of Biological Action

  A. K. Sirotkin, V. V. Zarubaev, L. N. Poznyiakova, M. A. Dumpis, T. D. Muravieva, T. K. Krisko, I. M. Belousova, O. I. Kiselev, L. B. Piotrovsky
  Fullerenes Nanotubes and Carbon Nanostructures 01/2006; Nanotubes(and Carbon Nanostructures):327-333. · 0.77 Impact Factor
• Article: Direct antiviral effect of cycloferon (10-carboxymethyl-9-acridanone) against adenovirus type 6 in vitro.

  V V Zarubaev, A V Slita, V Z Krivitskaya, A K Sirotkin, A L Kovalenko, N K Chatterjee
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  ABSTRACT: Adenoviruses represent a broad group of human pathogens that currently have no specific and safe drugs for treatment. We demonstrated direct (non IFN-mediated) antiviral activity of cycloferon (10-carboxymethyl-9-acridanone, CMA), a potent interferon inducer, against adenovirus type 6 (Ad6) in Hep-2 cells. Virus production and details of morphogenesis were studied by ELISA with antibodies to the Ad6 hexon protein, and transmission electron microscopy, respectively. Immunoenzyme assay revealed that CMA does not inhibit viral protein synthesis but instead strongly reduces the ability of the virus to generate infectious progeny virus in a dose dependent manner. Ultrastructural study shows that CMA alters the structure of intranuclear virus-specific inclusions. We suggest that CMA suppresses the late stages of viral cycle in the infected cell.
  Antiviral Research 05/2003; 58(2):131-7. · 4.30 Impact Factor
• Article: [Intracellular localization of cycloferon, its binding with DNA and stimulation of cytokines expression after exposure to cycloferon].

  A L Kovalenko, V I Kazakov, A V Slita, V V Zarubaev, V P Sukhinin
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  ABSTRACT: Despite the wide usage of immunomodulating preparates including interferon inducers in medical practice little is known about their mechanism of action. We investigated some theoretical aspects of action of potent interferon inducer--cycloferon (10-carboxymethyl-9-acridanone), such as intracellular localization, ability to DNA binding and cytokine expression stimulation. This preparate has been found to be localized in nuclei of monocytic cells U-937, T- and B-lymphocytes and HeLa cells. In Hep-2 line cycloferon was bound to cells from non-adhesive subpopulation and was not detected in cells of monolayer. Human fibroblasts did not bind the substance. Interaction with double-stranded but not with single-stranded DNA occurred at pH lower than 4.7 regardless of the GC-contain. As shown by dot-hybridization cycloferon stimulated the transcription of interferon-alpha gene in U-937 cells 29-44-fold compared to the control but did not affect the transcription of tumor necrosis factor and interleukin-2 genes. Our data allow to propose that some specific receptor exists in cell with affinity to cycloferon.
  Tsitologiia 02/2000; 42(7):659-64.
• Article: [The use of cycloferon in the therapy of experimental herpetic keratitis].

  V P Sukhinin, V M Pleskov, V V Zarubaev, A V Slita, E A Pestrinskaia, V V Brzheskiĭ, A L Kovalenko, F I Ershov
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  ABSTRACT: The cycloferon efficacy was investigated in the treatment of experimental herpesvirus kerato-conjunctivitis in rabbits. The model was demonstrated to reflect the main aspects of herpesvirus eye lesions in humans. Cycloferon application similarly to that of known interferon inducer poludan has been shown to enhance processes of inflammation and subsequent regeneration of eye tissues as well as to decrease mortality of animals due to the generalization of infection.
  Antibiotiki i khimioterapii͡a = Antibiotics and chemoterapy [sic] / Ministerstvo meditsinskoĭ i mikrobiologicheskoĭ promyshlennosti SSSR 02/2000; 45(6):13-6.
• Article: [Morphogenesis of chronic lung damage following administration of proteolytic enzymes].

  V V Zarubaev, V P Sukhinin
  Biulleten' eksperimental'noĭ biologii i meditsiny 08/1999; 128(7):115-9.
• Article: [Protective effect of cycloferon in experimental influenza].

  V P Sukhinin, V V Zarubaev, V G Platonov, A L Kovalenko, F I Ershov
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  ABSTRACT: Protective effect of granulated cycloferon has been studied in albino mice infected with influenza. The drug induced interferon production and prolonged the life span, decreased the mortality, suppressed the virus reproduction in the lungs, and decreased the infective activity of the virus. Morphologically the drug decreased the intensity of viral lesions in the bronchiolar epithelium, impeded the infection dissemination, and stimulated the productive (cellular) component of local inflammatory reaction. No influence on the development of chronic lesions in the lungs was detected.
  Voprosy virusologii 45(5):26-30.
• Article: [Antiviral activity of Ingavirin on an animal model for experimental disseminated adenovirus infection].

  V V Zarubaev, A V Slita, S V Beliaevskaia, V E Nebol'sin, O I Kiselev, D V Reĭkhart
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  ABSTRACT: Adenoviruses constitute a clinically important family of human pathogens. Due to their wide tissue tropism, adenoviruses are able to induce different diseases from moderate respiratory disorders to fatal outcomes in patients with immunodeficiencies. The authors present the results of a trial of the antiviral activity of the new drug Ingavirin [2-(imidazole-4-yl-ethanamide) pentandioic-1,5 acid] against human adenovirus type 5 on an animal model. Ingavirin is shown to decrease an adenoviral infectious titer in the liver and lung of neonatal Syrian hamsters (by approximately 1 log10 TCID50 as compared to the control) and to reduce the sizes of liver inflammation foci by 2-fold. Furthermore, it also decreases the count of virus-infected cells detectable by morphological analysis. Hepatocytes from Ingavirin-treated animals appear intact unlike strongly vacuolized cells from the animals given placebo. The findings make it possible to regard Ingavirin as a promising agent of the combination therapy of human adenovirus disease.
  Voprosy virusologii 56(6):23-7.
• Article: Direct antiviral effect of cycloferon (10-carboxymethyl-9-acridanone) against adenovirus type 6 in vitro

  V.V. Zarubaev, A.V. Slita, V.Z. Krivitskaya, A.K. Sirotkin, A.L. Kovalenko, N.K. Chatterjee
  [show abstract] [hide abstract]
  ABSTRACT: Adenoviruses represent a broad group of human pathogens that currently have no specific and safe drugs for treatment. We demonstrated direct (non IFN-mediated) antiviral activity of cycloferon (10-carboxymethyl-9-acridanone, CMA), a potent interferon inducer, against adenovirus type 6 (Ad6) in Hep-2 cells. Virus production and details of morphogenesis were studied by ELISA with antibodies to the Ad6 hexon protein, and transmission electron microscopy, respectively. Immunoenzyme assay revealed that CMA does not inhibit viral protein synthesis but instead strongly reduces the ability of the virus to generate infectious progeny virus in a dose dependent manner. Ultrastructural study shows that CMA alters the structure of intranuclear virus-specific inclusions. We suggest that CMA suppresses the late stages of viral cycle in the infected cell.
  Antiviral Research.
• Article: [Evaluation of metabolic parameters in vitro as a model for testing the cytotoxicity of antiviral drugs].

  O I Kiselev, E M Eropkina, T D Smirnova, M Iu Eropkin, E V Il'inskaia, V P Sukhinin, A P Prochukhanova, V V Zarubaev
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  ABSTRACT: A new test system based on in vitro assessment of the cellular viability and/or metabolism is proposed, which offers an informative approach to the screening of antiviral drugs. Cytotoxic effects of the antiviral drugs rimantadine and polyrem were studied on the cultures of some mammalian cells. The results of short-term (2 h) exposures with the drugs tested were close to their LD50 values in mammals, which makes the proposed test system promising for the assessment of drug toxicity in vivo for the whole organism. A study of the state of cell metabolism after a long-term (48 h) exposure showed that the system of endocytosis is more sensitive than other indices with respect to antiviral drugs. Is was demonstrated on the cell level that the binding of drugs into polymeric complexes can decrease the degree of its cytotoxicity: the toxicity of polyrem (a polymeric complex of rimantadine) was lower as compared to that of the equimolar concentration of rimantadine or a mixture of rimantadine with a polymeric carrier.
  Eksperimental'naia i klinicheskaia farmakologiia 69(1):65-70.
• Article: [Ultrastructural changes in the cells of human embryo lung fibroblasts in the reproduction of the coronavirus HCoV/SPb/01/03].

  A P Prochukhanova, A K Golovanova, A A Sominina, T D Smirnova, A K Sirotkin, V V Zarubaev
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  ABSTRACT: The reproduction of the new coronavirus HCoV/SPb/01/03 in the cultured human embryo lung fibroblasts (HELFBs) was electron microscopically studied. The virus was shown to replicate in the cultured HELFBs, by using for this a cell membrane system and causing profound changes in its morphology. After 24 hours of cell infection, there were mature and defective HCoVISPb/01/03 virions were detected in the vacuoles near the peripheral cisterns of the Golgi apparatus. Some of the vacuoles contained folded membranous structures along with virions.
  Voprosy virusologii 50(6):27-30.
• Article: [Effect of liposomal beta-carotene on experimentally lethal influenza infection].

  V P Sukhinin, V V Zarubaev, V G Platonov, S S Avtushenko
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  ABSTRACT: Effect of beta-carotene on experimental infection with A/Aichi/2/68 (H3B2) is studied in mice infected in an infective dose of 5-10 LD50. The drug notably decreased the mortality in experimental group in comparison with the control. Disease symptoms were less expressed and deaths observed later (7 days vs. 4 in the control) in mice treated with beta-carotene. Histological analysis of the lungs showed smaller foci of lesions. Metaplastic changes in the bronchial epithelium, typical of late terms of infection, were far less expressed in these animals. On the other hand, virus titers decreased negligibly in comparison with the control group. Electron-microscopic study of the effect of beta-carotene on virus population showed that virus replication in chick embryos in the presence of beta-carotene led to an increase in the percentage of filamentous and giant polygenome virus particles. The data indicate that beta-carotene is a promising drug for prevention and treatment of influenza.
  Voprosy virusologii 44(4):163-7.
• Article: [Reticuloendothelial system and persistence of influenza virus in the body].

  V M Pleskov, V V Zarubaev, Iu V Pleskova
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  ABSTRACT: The method of in situ transcription was used to detect influenza virus genome in the organs of infected mice. Virus-specific RNA was found in the alveolar macrophages 5 months after infection, this confirming the capacity of the virus to persist in vivo in these cells for a long time. Evidence in favor of influenza virus modification in an infected host body is presented, which fact dramatically affects virus interactions with macrophages. Problems in the development of acute and persistent infections and influenza virus persistence in reticuloendothelial cells are discussed.
  Voprosy virusologii 41(2):53-8.
• Article: [Effect of a combination of glutamyl-tryptophan and glycyrrhizic acid on the course of acute infection caused by influenza (H3H2) virus in mice].

  V S Smirnov, V V Zarubaev, P M Anfimov, A A Shtro
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  ABSTRACT: The purpose of the study was to evaluate the modulating effect of glutamyl-tryptophan (EW), glycyrrhizic acid (GA), and their combination on the course of experimental infection caused by influenza A (H3N2) virus in mice. The animals were infected with influenza A/Aichi/2/68 (H3N2) virus in a dose of 1 or 10 LD50. GA (10 mg/kg body weight) and EW (0.1, 10, and 1000 microg/kg) alone or in combination were intraperitoneally injected for 5 days, starting on day 1 of virus infection. Rimantadine 50 mg/kg/day was used as a comparison drug. The combination of EW (1000 microg/kg) and GA (10 mg/kg) was ascertained to exert the maximum protective effect manifesting itself in reducing the death of infected animals (by 75-79% compared to the control depending on the viral dose) and the titers of viruses accumulated in the lung (5-6 log EID50) and in preventing lung tissue edema and inflammation. The noted effect was comparable with that seen in the use of rimantadine. The agents used alone had a lower efficacy than rimantadine. The findings permit the combination of GA and EW to be considered to be a promising agent for the treatment of influenza.
  Voprosy virusologii 57(3):23-7.
• Article: [Ingavirin treatment of experimental parainfluenza pneumonia in Syrian hamsters].

  V V Zarubaev, A V Garshinina, N A Kalinina, S V Beliaevskaia, V E Nebol'sin, O I Kiselev, D V Reĭkhart
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  ABSTRACT: Parainfluenza viruses affect the upper respiratory tract in all age group patients, in children aged 6 months to 3 years in particular. The most urgent task is to design drugs to treat parainfluenza. This investigation studied the antiviral activity of Ingavirin (2-(imidazole-4-yl) ethanamide of pentandioic-1,5 acid) on a model of parainfluenza infection in Syrian hamsters. The drug was shown to restrict the infectious process in animal lung tissue. This restriction manifested itself as reductions in the infectious titer of parainfluenza virus in the lung tissue, in the degree of pulmonary edema and tissue cell infiltration, and in virus-specific lesion of bronchial epithelial cells. The in vitro experiments demonstrated the ability of Ingavirin to diminish the infective activity of viral descendants. The finding allows one to consider Ingavirin to be a promising antiviral agent that is active against parainfluenza infection in vivo.
  Voprosy virusologii 57(2):35-9.
• Article: [Effect of Ingavirin on the ultrastructure of the morphogenesis of adenovirus infection in vivo].

  V V Zarubaev, A V Slita, A K Sirotkin, S V Beliavskaia, V E Nebol'sin, D V Reĭkhart, O I Kiselev
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  ABSTRACT: The goal of this study was to evaluate the effect of Ingavirin on the morphological features of the foci of adenovirus hepatitis in Syrian hamsters by electron microscopy. The use of the drug was shown to cause a substantial reduction in the rate of destructive processes and inflammatory reactions in the liver, by normalizing its structure at the levels of both tissue and individual hepatocytes. After administration of Ingavirin, the morphogenesis of adenovirus infection in the infected hepatocytes did not differ from that in the controls; however, the infected cells were fewer. The proportion of morphologically inadequate virions in the presence of Ingavirin increased from 35 to 46%. The findings suggest that Ingavirin is an effective drug that has antiviral, anti-inflammatory, and cytoprotective activities in the focus of adenovirus tissue involvement.
  Voprosy virusologii 57(3):17-23.
• Article: [In vitro and in vivo effects of ingavirin on the ultrastructure and infectivity of influenza virus].

  V V Zarubaev, S V Beliaevskaia, A K Sirotkin, P M Anfimov, V E Nebol'sin, O I Kiselev, D V Reĭkhart
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  ABSTRACT: The aim of this investigation was to study the effect of ingavirin on the structure and properties of influenza virions forming in its presence. The infectious activity of the virus and the morphology of the virions were analyzed by titration in cell culture and electron microscopy, respectively. The use of ingavirin was shown to reduce the proportion of morphologically intact virions and to increase that of filamentous and giant particles. No defects of surface glycoproteins were observed. The effect of the drug did not depend on the chosen model of virus replication and it was similarly shown in both cultured human cells and laboratory animals. In MDCK and A549 cells and in the mouse lungs, viral infectious activity was decreased by 1-2 orders of magnitude in relation to a model. The findings suggest that Ingavirin is able to impair the processes of viral morphogenesis, which in turn leads to a reduction in the infectivity of progeny virions.
  Voprosy virusologii 56(5):21-5.