[Modification of hematosupressive action of ionizing radiation by dicarbamine].

There was studied the effect of different doses of Dicarbamine by means of oral medical-prophylactic and medical administration on the peripheral blood of rabbits in conditions of experimental radiation damage to the blood system. The drug provided the safety of circulating red blood cells at rather high level, prevented the development of severe post-radiation thrombocytopenia, reduced post-radiation leukocytopenia, accelerated processes of recovery of peripheral blood leukocytes to the initial level by segmented neutrophils and lymphocytes.

[Comparative study of the hemato-protective effect of Dicarbamine and Leykostime in experimental radiation damage to the blood system].

There was studied the influence Dicarbamine and Leykostime on peripheral blood leukocyte composition of rabbits in experimental radiogenic damage to the blood system. Dicarbamine significantly insured the safety of circulating red blood cells, prevented the development of severe postradiation thrombocytopenia, reduced postradiation leukocytopenia, and accelerated the recovery of peripheral blood leukocytes to the initial level by segmented neutrophils and lymphocytes. Leukostime ensured the safety of peripheral blood leukocytes however was less effective than Dicarbamine to prevent postradiation deficit of circulating red blood cells and thrombocytes.

[A comparative study of the myeloprotective effect of dicarbamine and leucostim in experimental post-radiation bone marrow syndrome].

We studied the effect of dicarbamine and leucostim on myelopoiesis in experimental post-radiation bone marrow syndrome. Dicarbamine in different modes of administration and doses provided a high level of protection of proliferating hematopoietic precursors in the early period after radiation, which was reflected in a statistically significant decrease in the depth and duration of post-radiation deficit of cells, such as of granulocytes, lymphocytes, megakaryocytes and erythroid cells. The greatest effect of the drug appeared at a dose of 4 mg/kg (prophylactic administration) and a dose of 15 mg/kg (curative double dose). In the bone marrow of experimental animals leucostim prevented development of post-radiation deficit of granulocytes and lymphocytes to a lesser extent, than dicarbamine, and it was effective for erythroid cells and megakaryocytes.

[In vitro investigation of the antiviral activity of Ingavirin against human metapneumovirus].

The antiviral activity of Ingavirin against human metapneumovirus (HMPV) infection was investigated in vitro. The investigation used the human cell line ChangConjunctiva, permissive for HMPV, clone 1-5C4, and the HMPV strain isolated at the D. I. Ivanovsky Research Institute of Virology. The experimental studies suggest that when added at a concentration of 50 to 500 microg/ml to a nutrient medium 24 hours after HMPV infection, Ingavirin suppressed effectively virus replication by 2.2-3.3 logs, respectively. When used at a concentration of 500 microg/ml 24 hours before cell infection, Ingavirin protected cells from HMPV infection.

[Effect of Ingavirin on the ultrastructure of the morphogenesis of adenovirus infection in vivo].

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.

[Ingavirin treatment of experimental parainfluenza pneumonia in Syrian hamsters].

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.

[Hematoprotective effectiveness of dicarbamin in experimental post-radiation bone marrow syndrome].

The effect of dicarbamin on cellular composition of rabbits' venous blood in experimental post-radiation bone marrow syndrome was studied. The dicarbamin use has allowed to reduce depth and to shorten the duration of post-radiation leukocytopenia.

[Effect of dicarbamine on medullary hemopoiesis in experimental post-irradiation bone-marrow syndrome].

The effect of dicarbamine on hemopoiesis in experimental post-irradiation bone-marrow syndrome was studied. The myeloprotective activity of the drug was established. It manifested in the protection of hematopoietic progenitor cells and stimulation of cell proliferation and differentiation in the bone marrow.

[In vitro and in vivo effects of ingavirin on the ultrastructure and infectivity of influenza virus].

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.

[Antiviral activity of Ingavirin on an animal model for experimental disseminated adenovirus infection].

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.

[In vitro and in vivo efficacy of Ingavirin against strains of pandemic influenza virus A(H1N1/09)v].

AIM: To study efficacy of Ingavirin in vitro and in vivo against strains of pandemic influenza virus A(H1N1/09)v and influenza virus A(H5N1) and A(H3N2). MATERIALS AND METHODS: Changes in hemagglutinating and cytopathic activity of influenza virus strains A(H1N1/09)v, A(H5N1) and A(H3N2) during their incubation in the presence of Ingavirin or Remantadin on MDCK cell culture were studied. In mice infected by influenza strains A(H1N1/09)v and A(H3N2) and orally treated with Ingavirin, Tamiflu or Remantadin virus titers in lungs were measured. RESULTS: There was decrease in hemagglutinating and cytopathic activity of influenza virus strains after incubation with Ingavirin in vitro. Ingavirin effectively inhibited reproduction of influenza virus strains A(H1N1/09)v and A(H3N2) in lungs of infected mice. Titers of these strains in lung homogenates decreased when Ingavirin was orally administered to infected mice. CONCLUSION: Strains of influenza virus A(H1N1/09)v were susceptible to Ingavirin and Tamiflu but resistant to Remantadin. Reference strains of A(H5N1) and A(H3N2) were susceptible to Ingavirin, Tamiflu and Remantadin.

[Effect of the antiviral drug Ingaviruin on intracellular transformations and import into the nucleus of influenza A virus nucleocapsid protein].

The paper presents the results of studying the effect of the antiviral drug Ingavirin on different stages of intracellular transformations of influenza A virus nucleocapsid protein (NP). Ingavirin 400-1000 microg/ml has been found to impair the biogenesis of influenza virus NP, to lower the efficiency of formation of conformationally mature compact NP oligomers, and to retard the migration of newly-synthesized NP from the cytoplasm to the nucleus. It is shown that there is an association of tritium-labeled Ingavirin with the nuclear membranes of MDCK cells. The investigations of the mechanisms of antiviral activity of Ingavirin are not only important for the characterization of this drug, but also promote the detection of potential targets to design novel antiviral agents.

[Growth dynamics of transplantable murine tumors in the course of dicarbamin-protected chemotherapy].

Dicarbamin-assisted mono- and combination chemotherapy (cyclophosphamide + carboplatin + cisplatin) for transplantable tumors born by linear or hybrid mice of both sexes was investigated. It was shown that long-term oral administration contributed to the effect of a range of cytostatic therapeutic dosage rather than adversely affected it. Our findings were used to make a case for clinical studies of dicarbamin for its potential of lowering hematological toxicity of antitumor therapy.

[Experimental investigation of Ingavirin antiviral activity against human parainfluenza virus].

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.

[Prophylactic and therapeutic efficacies of Ingavirin, a novel Russian chemotherapeutic, with respect to influenza pathogen A (H5N1)].

The experimental study of the Ingavirin efficacy against the influenza virus A (H5N1) on intranasally-infected albino mice vs. Tamiflue and Arbidol showed that when used for the prophylaxis, urgent prophylaxis and therapy it was effective in the protectiom of the animals from death. The efficient dose for the prophylaxis of the influenza infection was 5 mg/kg (protective efficacy of 46.7%) and for the urgent prophylaxis and therapy it was 15 mg/kg (protective efficacy of 40.0 and 35.0% respectively).

[Antiviral activity of Ingavirin in experimental lethal influenza due to influenza virus B in albino mice].

The protective activity of Ingavirin against experimental infection caused by influenza B virus was studied on albino mice vs. Arbidol. Oral use of Ingavirin was shown to decrease the infectious titers of the virus in the animal lung tissue, to normalize the body weight dynamics, to lower the mortality and to increase the average lifespan vs. the placebo-treated animals. The activity of Ingavirin was higher than that of the reference drug. The results allowed to consider Ingavirin as a prospective agent for the treatment of influenza infection in humans.

[Experimental study of Ingavirin antiviral activity against human adenovirus].

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.

[In vitro efficacy of Ingavirin against the pandemic influenza virus A(H1N1/09)v].

Ingavirin was shown to be efficient in inhibition of the influenza virus strains A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009 (H1N1)v and A/Moscow/226/2009 (H1N1)v, as well as the strains A/Chicken/Kurgan/05/2005 (H5N1) and A/Aichi/2/68 (H3N2) in the MDCK cell culture. The hemagglutinin and cytopathic activity of the influenza virus strains decreased at entering Ingavirin in vitro.

[Protective activity of Ingavirin in experimental lethal influenza due to pandemic influenza virus A (H1N1)v in albino mice].

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.

[In vivo efficacy of Ingavirin against pandemic A (H1N1/09)v influenza virus].

Ingavirin was shown to be efficient in inhibition of the pandemic influenza virus strains A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009 (H1N1)v and A/Moscow/226/2009 (H1N1)v. as well as the influenza virus strain A/Aichi/2/68 (H3N2) in the lungs of the infected mice. After oral administration of Ingavirin the titers of the influenza virus strains in the lung homogenates lowered.