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1.
Russ Chem Bull ; 72(3): 807-818, 2023.
Article in English | MEDLINE | ID: mdl-37089866

ABSTRACT

Efficient conditions for the synthesis of nitrogen-containing heterocyclic derivatives of (1R,3S)(+)-camphoric acid were selected. A series of heterocyclic compounds based on (+)-camphoric acid bearing pharmacophoric fragments was synthesized using the developed methodology. The compounds were tested for their antiviral activity against SARS-CoV-2 and H1N1 influenza viruses, and efficient inhibitors were identified that are of significant interest for further studies. The stability of the compounds and pharmaco-kinetics of the leader compound were studied when administered intragastrically and intramuscularly to mice at a dose of 200 mg kg-1 using the HPLC-MS/MS method.

2.
Russ Chem Bull ; 71(11): 2473-2481, 2022.
Article in English | MEDLINE | ID: mdl-36569656

ABSTRACT

A comparative evaluation of the antiviral activity of a number of new and previously synthesized terpenophenols and their N- or O-containing derivatives against the A/Puerto Rico/8/34 (H1N1) virus strain was carried out. 2-Isobornylphenol, 1,2-dihydroxy-6-isobornyl-4-methylbenzene, 2-isobornyl-1,4-benzoquinone, and N-butyl-4-hydroxy-3,5-diisobornylbenzamide showed the highest activity.

3.
Russ Chem Bull ; 71(11): 2460-2466, 2022.
Article in English | MEDLINE | ID: mdl-36569657

ABSTRACT

A new method for preparation of 4-hydroxy-3-nitro-1,4-dihydrotriazolo[5,1-c][1,2,4]-triazines using 1-nitro-2-morpholinoethylene and 3-diazo-1,2,4-triazoles is proposed. Antiviral activity against the Coxsackie B3 virus and electrochemical transformations of the prepared compounds are studied.

4.
Dokl Biochem Biophys ; 506(1): 227-230, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36303058

ABSTRACT

New copolymers of vinylphosphonic acid (VPA) with 2-deoxy-2-methacrylamido-D-glucose, 4-acryloylmorpholine (4-AM), and acrylamide have been synthesized, and their antiviral activity against influenza virus has been studied in in vitro and in vivo experiments. Optimal antiviral characteristics and low cytotoxicity were exhibited by the copolymer of VPA with 4-AM, composition 56 : 44 mol %, molecular weight 33 000. The polymer exhibited virus-inhibiting properties with an IC50 = 1 µg/mL and a selectivity index of 302. Prophylactic intranasal administration of the polymer in a murine model of influenza pneumonia completely prevented the virus-induced death of animals, whereas the level of mortality in the placebo group was 90%. The results of this study indicate a high antiviral potential of polymeric compounds based on VPA.


Subject(s)
Organophosphonates , Polymers , Mice , Animals , Polymers/pharmacology , Organophosphonates/pharmacology , Vinyl Compounds , Antiviral Agents/pharmacology
5.
Bioorg Med Chem Lett ; 30(13): 127216, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32360104

ABSTRACT

Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.


Subject(s)
Antioxidants/pharmacology , Antiviral Agents/pharmacology , Polyphenols/pharmacology , Triazines/pharmacology , Triazoles/pharmacology , Animals , Antioxidants/chemical synthesis , Antioxidants/metabolism , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Dogs , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Influenza A virus/drug effects , Madin Darby Canine Kidney Cells , Microbial Sensitivity Tests , Molecular Docking Simulation , Polyphenols/chemical synthesis , Polyphenols/metabolism , Protein Binding , Triazines/chemical synthesis , Triazines/metabolism , Triazoles/chemical synthesis , Triazoles/metabolism
6.
Ter Arkh ; 92(11): 45-50, 2020 Dec 26.
Article in Russian | MEDLINE | ID: mdl-33720603

ABSTRACT

Influenza and ARVI represent the most numerous and dangerous group of causative agents of respiratory infections human. AIM: Characterization of the antiviral properties of enisamium iodide against human respiratory viruses in in vitro experiments. MATERIALS AND METHODS: In the course of experiments, the cytotoxic properties of enisamium iodide were studied against the cell lines Vero, MA-104, A549, L-41 and HEp-2. The antiviral activity of enisamium iodide was studied using virus yield reduction assay against influenza viruses, parainfluenza virus, respiratory syncytial virus, Coxsackie B3 and Coxsackie B4 viruses, as well as adenoviruses types 5 and 6. RESULTS: The most sensitive to the action of enisamium iodide was the human parainfluenza virus, whose activity decreased by 2.3 orders of magnitude under the action of the drug in A549 cells. Of the cell cultures used, enisamium iodide exhibited the maximum antiviral effect in human lung carcinoma cells A549, where, in its presence, the level of reproduction of adenoviruses of types 5 and 6, Coxsackie viruses B3 and B4, and human parainfluenza virus decreased by an order of magnitude or more. The antiviral activity of enisamium iodide was least manifested in Vero cells. CONCLUSION: According to the results of in vitro experiments, enisamium iodide can be considered as an antiviral drug with a wide spectrum of activity against human respiratory viruses.


Subject(s)
Influenza, Human , Viruses , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cell Line , Chlorocebus aethiops , Humans , Influenza, Human/drug therapy , Iodides/therapeutic use , Pyridinium Compounds , Vero Cells
7.
Photodiagnosis Photodyn Ther ; 25: 35-42, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30412780

ABSTRACT

Photophysical and in vitro photocytotoxicity studies were performed for the photosensitizer Dimegine, a disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX with very low systemic toxicity. The singlet oxygen and luminescence quantum yield were ΦΔ = 0,65 ± 0,06, and Φƒ=0,11 ± 0,01 respectively, and were independent of the excitation wavelength. The photobleaching coefficients for Dimegine dissolved in phosphate buffer (pH 7.4), and DMEM medium at concentration 2 µM/l and in phosphate buffer (pH 7.0) at concentration 10 µM/l were 16·10-5, 9·10-5 and 2·10-5 respectively. In vitro cellular distribution and photocytotoxicity was studied in two human (U87 - primary glioblastoma and HT1376 - bladder cancer) and two rat cell lines (RG2 - glioma, and AY27 - bladder carcinoma). Fluorescence microscopy analysis shows primary Dimegine accumulation as small fluorescent inclusion bodies around the nuclei, suggesting an apoptotic over a necrotic cell death mechanism. The PDT efficacy was slightly higher for the rat cell lines over the human-derived cell lines, with LD50 values of 2,5 µM/l, 2.8 µM/l, 4.5 µM/l, 2.8 µM/l using 530 nm excitation wavelength for AY27, RG2, HT1376 and U87 respectively, and 1.8 µM/l, 2 µM/l, 5 µM/l, 2.4 µM/l using 625 nm excitation wavelength for AY27, RG2, HT1376 and U87 respectively. Comparison to literature data showed that Dimegine demonstrated improved phototherapeutic characteristics comparing to PpIX-mediated PDT.


Subject(s)
Deuteroporphyrins/pharmacology , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Singlet Oxygen/metabolism , Animals , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Hydrogen-Ion Concentration , Methylene Blue/pharmacology , Microscopy, Fluorescence , Photobleaching/drug effects , Protoporphyrins/pharmacology , Rats
8.
Mol Biol (Mosk) ; 51(6): 927-937, 2017.
Article in Russian | MEDLINE | ID: mdl-29271957

ABSTRACT

Seasonal and highly infectious strains of the influenza A and influenza B viruses cause millions of cases of severe complications in elderly people, children, and patients with immune diseases each year. Immunoglobulin A (IgA), which is an active component of humoral immunity, can prevent the spread of the virus in the upper respiratory tract. The preparation and study of the properties of recombinant virus-specific IgA could be an important approach to finding new means of preventing and treating influenza. Based on CHO DG44 cells, we developed stable monoclonal cell lines that produce monomeric and dimeric antibodies FI6-IgA1 and FI6-IgA2m1 to hemagglutinin (HA) of the influenza A virus. When studying the productivity, growth, and stability of the obtained clones, we found that the dimeric form of antibodies of IgA1 isotype is superior to other forms. The dimeric form of IgA antibodies plays a key role in mucosal immunity. Recognizing the prospects of using dimeric IgA as prophylactic and therapeutic mucosal drugs for viral infections, we studied their virus-neutralizing and antiviral activities on MDCK cell culture and compared them with the antibodies of the IgG1 isotype. This study presents the data on antiviral and virus-neutralizing activities of the FI6-IgA1 dimers to seasonal and highly infectious strains of influenza A virus.


Subject(s)
Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , Antiviral Agents/pharmacology , Immunoglobulin A/pharmacology , Immunoglobulin G/pharmacology , Influenza A virus/drug effects , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/genetics , Antibodies, Viral/biosynthesis , Antibodies, Viral/genetics , Antiviral Agents/chemistry , Antiviral Agents/metabolism , CHO Cells , Cricetulus , Dogs , Gene Expression , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Immunoglobulin A/biosynthesis , Immunoglobulin A/genetics , Immunoglobulin G/biosynthesis , Immunoglobulin G/genetics , Influenza A virus/growth & development , Influenza A virus/immunology , Madin Darby Canine Kidney Cells , Neutralization Tests , Protein Multimerization , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/pharmacology
9.
Medchemcomm ; 8(5): 960-963, 2017 May 01.
Article in English | MEDLINE | ID: mdl-30108810

ABSTRACT

Herein, we present the design and synthesis of a series of novel heterocyclic derivatives of (-)-borneol and (-)-isoborneol as potent inhibitors of the influenza A virus. All compounds were tested for their toxicity against MDCK cells and for virus-inhibiting activity against the influenza virus A/Puerto Rico/8/34 (H1N1). Compounds 7, 16 and 26 containing a morpholine fragment exhibited the highest efficiency as agents inhibiting the replication of the influenza virus A(H1N1) with selectivity indices of 82, 45 and 65, correspondingly. Derivatives 9 (SI = 23) and 18 (SI = 25) containing a 1-methylpiperazine motif showed moderate antiviral activity. Structure-activity analysis of this new series of borneol derivatives revealed that a 1,7,7-trimethylbicyclo[2.2.1]heptan scaffold is required for the antiviral activity.

10.
Vopr Virusol ; 61(1): 27-31, 2016.
Article in Russian | MEDLINE | ID: mdl-27145597

ABSTRACT

A study of the antiviral activity of antioxidants against viral infections is believed to be essential for creating complex antiviral agents. Dihydroquercetin is considered as the most active antioxidant extracted from Larix gmelinii. In this work, we present results of experiments of the antiviral properties of dihydroquercetin against a member of the family Picarnaviridae--Coxsackievirus B4 in vitro. We have estimated that dihydroquercetin reduces viral titers at 100 µg/ml concentration as compared with control of virus. We have shown using the plaque assay that CPE of virusis reduced in the presence of dihydroquercetin at 100 µg/ml. Study of the phase of viral lifecycle, in which dihydroquercetin acted, demonstrated that the highest efficacy of the antiviral therapy was reached at early stages of virus reproduction (1-3 hours post infection). These results show that dihydroquercetin has antiviralproperty against Coxsackievirus B4. This drug and other antioxidants can be tested as inhibitors of viral replication.


Subject(s)
Antioxidants/pharmacology , Antiviral Agents/pharmacology , Enterovirus B, Human/drug effects , Quercetin/analogs & derivatives , Virus Replication/drug effects , Animals , Antioxidants/isolation & purification , Antiviral Agents/isolation & purification , Chlorocebus aethiops , Enterovirus B, Human/physiology , Larix/chemistry , Quercetin/isolation & purification , Quercetin/pharmacology , Vero Cells , Viral Load/drug effects
11.
Vopr Onkol ; 62(1): 138-45, 2016.
Article in Russian | MEDLINE | ID: mdl-30444592

ABSTRACT

Malignant glioma is the most frequently occurring primary brain tumor. Despite significant progress in the diagnostics and treatment of neoplastic diseases the prognosis for patients with III-IV grade gliomas, remains extremely unfavorable. Rapidly developing area in oncology is the employment of therapeutic viruses with natural or genetically engineered oncolytic activity. In the present study we demonstrated the oncolytic potential of a recombinant influenza A virus vector with impaired interferon antagonism function of NS1 protein in treatment of malignant glioma. Recombinant influenza A virus (HA-DS-GFP) expressing green fluorescent protein from the NS1 open reading frame was used as a model vector. HA-DS-GFP virus has shown infectivity towards glioma cells both in vitro, and in vivo (experimental glioma model in rats). Intratumoral inoculation of HA-DS-GFP resulted in a substantial inhibition or complete regression of tumor growth. Our data demonstrate that recombinant influenza vectors have promising potential in therapy of malignant gliomas.


Subject(s)
Glioma/therapy , Influenza A virus , Neoplasms, Experimental/therapy , Oncolytic Virotherapy , Oncolytic Viruses , Animals , Cell Line, Tumor , Female , Glioma/genetics , Glioma/metabolism , Humans , Neoplasms, Experimental/genetics , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Rats
12.
Vopr Virusol ; 61(3): 125-131, 2016 Jun 28.
Article in Russian | MEDLINE | ID: mdl-36494946

ABSTRACT

In this work, the activity of glycyrrhizic acid (GL) and dipeptide alpha-glutamyl-tryptophane (EW) as single preparations or in combination (GL+EW) against experimental adenoviral infection in the syrian hamsters was studied. Application of gl and GL+EW was shown to decrease the level of the adenovirus replication in liver tissue by 0.6 - 1.2 lgTCID50 depending on the composition and time point of the post infection. It was also demonstrated that normalization of the structure of the liver tissue was required, which was shown on the level of both optical and electron microscopy. The results obtained in this work suggest that gl and GL+EW may be considered as potential component of the complex therapy of adenoviral infection.

13.
Antiviral Res ; 120: 126-33, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26072310

ABSTRACT

Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we report anti-influenza activity of camphor derivative 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol (camphecene). In in vitro experiments it inhibited influenza viruses A(H1, H1pdm09, H3 and H5 subtypes) and B with EC50's lying in micromolar range. Due to low cytotoxicity it resulted in high selectivity indices (74-661 depending on the virus). This effect did not depend on susceptibility or resistance of the viruses to adamantane derivatives amantadine and rimantadine. The compound appeared the most effective when added at the early stages of viral life cycle (0-2h p.i.). In direct hemagglutinin inhibition tests camphecene was shown to decrease the activity of HA's of influenza viruses A and B. The activity of camphecene was further confirmed in experiments with influenza virus-infected mice, in which, being used orally by therapeutic schedule (once a day, days 1-5 p.i.) it decreased specific mortality of animals infected with both influenza A and B viruses (highest indices of protection 66.7% and 88.9%, respectively). Taken together, these results are encouraging for further development of camphecene-based drug(s) and for exploration of camphor derivatives as highly prospective group of potential antivirals.


Subject(s)
Antiviral Agents/administration & dosage , Camphor/analogs & derivatives , Camphor/administration & dosage , Ethanolamines/administration & dosage , Hemagglutinins/metabolism , Influenza A virus/drug effects , Influenza B virus/drug effects , Administration, Oral , Animals , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Camphor/adverse effects , Camphor/pharmacology , Cell Survival/drug effects , Disease Models, Animal , Drug Evaluation, Preclinical , Ethanolamines/adverse effects , Ethanolamines/pharmacology , Female , Mice, Inbred BALB C , Microbial Sensitivity Tests , Orthomyxoviridae Infections/drug therapy , Survival Analysis , Treatment Outcome
14.
Arkh Patol ; 77(2): 22-27, 2015.
Article in Russian | MEDLINE | ID: mdl-26027395

ABSTRACT

OBJECTIVE: to assess the potential role of influenza virus in fatal pneumonia during the epidemic and interepidemic periods. MATERIAL AND METHODS An immunohistochemical method was used to clinically and morphologically analyze 40 fatal outcomes of acute pneumonias in 2009-2013. Laboratory tests could not establish the diagnosis of influenza in 20 cases of the study group with clinical and/or morphological pattern of this illness. Seventeen cases occurred during the epidemic period (autopsies from November 2009 to January 2010) and the seasonal rise of morbidity; 3 cases were observed during the interepidemic period. A control group was additionally formed from 20 cases with neither clinical nor further morphological evidence of suspected influenza in the presence of pneumonia in both the epidemic and interepidemic periods. RESULTS: In the study group, influenza virus nucleoprotein was detected by immunohistochemistry (IHC) in the bronchial epithelial cells with the signs of cytopathic changes in half of the cases and that in the alveolocytes in 30%. Sporadic cases displayed a positive IHC response of blood vessel endothelial cells, which was attended by staining of the epithelium and macrophages. The maximum disease periods with the virus nucleoprotein being detected by IHC in the macrophages doubled those in the epithelial cells (40 versus 22 days). The control group showed a large number of cases with a positive macrophage response that was approximately similar to that in the study group. Despite the frequent detection and intensive staining of macrophages, they demonstrated no cytopathic changes, which can be explained by the low virulence persistence of influenza virus in the macrophages. CONCLUSION: These investigations showed the role of influenza virus in the occurrence of additional deaths in the epidemic period and a possible fatal outcome in the interepidemic period.


Subject(s)
Epidemics , Influenza, Human/diagnosis , Influenza, Human/mortality , Lung/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Cytopathogenic Effect, Viral , Humans , Immunohistochemistry , Influenza A virus/isolation & purification , Influenza A virus/pathogenicity , Influenza, Human/pathology , Influenza, Human/virology , Logistic Models , Lung/pathology , Mortality/trends , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Russia/epidemiology , Virulence
15.
Antivir Chem Chemother ; 24(3-4): 92-8, 2015 08.
Article in English | MEDLINE | ID: mdl-27022094

ABSTRACT

BACKGROUND: Influenza is a disease of significant morbidity and mortality, the number of anti-influenza drugs is small; many of them stimulate the appearance of resistant strains. In this work, we demonstrate activity of some usnic acid (UA) derivatives against influenza virus in vitro and in vivo. METHODS: Organic synthesis was used to prepare compounds. Antiviral activity of the compounds in vitro was evaluated by their ability to decrease the virus titer on Madin-Darby Canine Kidney cells. In vivo activity was evaluated by decrease of mortality and index of protection. RESULTS: Compounds were tested against a broad spectrum of influenza virus strains and showed activity against all used strains. One compound, [5] (valine enamine of UA), also significantly reduced lethality of infected animals and does not give rise to the appearance of resistant strains. Additional studies showed that hepatotoxicity of compound [5] is reduced comparatively to UA. CONCLUSION: Our results suggest that valine enamine of UA could be a potential candidate for the development of a new anti-influenza therapy.


Subject(s)
Antiviral Agents/pharmacology , Benzofurans/pharmacology , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Orthomyxoviridae/drug effects , Animals , Antiviral Agents/administration & dosage , Benzofurans/administration & dosage , Cell Survival/drug effects , Dogs , Dose-Response Relationship, Drug , Female , Hepatocytes/drug effects , Hepatocytes/pathology , Madin Darby Canine Kidney Cells/drug effects , Madin Darby Canine Kidney Cells/virology , Mice , Mice, Inbred Strains , Microbial Sensitivity Tests , Orthomyxoviridae Infections/prevention & control , Structure-Activity Relationship
16.
Antiviral Res ; 113: 4-10, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25446335

ABSTRACT

This study is devoted to the antiviral activity of peptide fragments from the PB1 protein - a component of the influenza A RNA polymerase. The antiviral activity of the peptides synthesized was studied in MDCK cell cultures against the pandemic influenza strain A/California/07/2009 (H1N1) pdm09. We found that peptide fragments 6-13, 6-14, 26-30, 395-400, and 531-540 of the PB1 protein were capable of suppressing viral replication in cell culture. Terminal modifications i.e. N-acetylation and C-amidation increased the antiviral properties of the peptides significantly. Peptide PB1 (6-14) with both termini modified showed maximum antiviral activity, its inhibitory activity manifesting itself during the early stages of viral replication. It was also shown that the fluorescent-labeled analog of this peptide was able to penetrate into the cell. The broad range of virus-inhibiting activity of PB1 (6-14) peptide was confirmed using a panel of influenza A viruses of H1, H3 and H5 subtypes including those resistant to oseltamivir, the leading drug in anti-influenza therapy. Thus, short peptide fragments of the PB1 protein could serve as leads for future development of influenza prevention and/or treatment agents.


Subject(s)
Influenza A Virus, H1N1 Subtype/drug effects , Influenza A virus/drug effects , Peptide Fragments/pharmacology , RNA-Dependent RNA Polymerase/chemistry , Viral Proteins/chemistry , Amino Acid Sequence , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Dogs , Influenza A Virus, H1N1 Subtype/physiology , Influenza A virus/physiology , Madin Darby Canine Kidney Cells , Molecular Sequence Data , Oseltamivir/pharmacology , Peptide Fragments/chemical synthesis , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Virus Replication/drug effects
17.
Tsitologiia ; 56(3): 241-7, 2014.
Article in Russian | MEDLINE | ID: mdl-25509421

ABSTRACT

Influenza is a respiratory infection widely spread around the world. Influenza complications are various in nature and in most cases involve the excessive proliferation of cells in respiratory tract as a factor of pathogenesis. In the present work the efficacy of the use of apoptosis inducer 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalenecarboxylic acid (AHPN) for prophylaxis of chronic damage on the stage of post- influenza pneumonia has been studied. Mice were infected with influenza virus A/mallard/Pennsylvania/10218/84(H5N2) with further study of the level of influenza virus reproduction in the lungs, specific mortality of animals and morphology of the foci of post-influenza pneumonia on the 15th day post inoculation. AHPN was shown to decrease the infectious activity of the virus in the lungs by 1.2-1.5 log10 EID50/0.2 mL depending on the dose as compared to the control group, in a weak decrease in mortality of animals (protection index was 12.5-37.5%). The application of AHPN restricted both the proliferative and infiltrative component in chronic post-influenza lesions. It demonstrated the most pronounced effect on the lung morphology when applied on days 4 to 7 post inoculation, i. e. in the period of maximal activation of inflammatory tissue infiltration and regeneration of bronchiolar epithelium. In conclusion, the use of apoptosis inducers can partially prevent the development of chronic post-influenza lesions with proliferative component.


Subject(s)
Antineoplastic Agents/pharmacology , Epithelial Cells/drug effects , Lung/drug effects , Orthomyxoviridae Infections/drug therapy , Pneumonia, Viral/drug therapy , Respiratory Mucosa/drug effects , Retinoids/pharmacology , Animals , Apoptosis/drug effects , Cell Proliferation , Dose-Response Relationship, Drug , Epithelial Cells/pathology , Epithelial Cells/virology , Influenza A Virus, H5N2 Subtype/drug effects , Influenza A Virus, H5N2 Subtype/growth & development , Lung/pathology , Lung/virology , Mice , Orthomyxoviridae Infections/complications , Orthomyxoviridae Infections/mortality , Orthomyxoviridae Infections/pathology , Pneumonia, Viral/etiology , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Respiratory Mucosa/pathology , Respiratory Mucosa/virology , Survival Analysis , Time Factors , Viral Load/drug effects , Virus Replication/drug effects
18.
Photodiagnosis Photodyn Ther ; 11(2): 165-70, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24583281

ABSTRACT

BACKGROUND: The problem of transfusion-transmitted infections still remains serious and actual for health care despite the detailed testing of donors. Human immunodeficiency virus, hepatitis B and C viruses and human cytomegalovirus are among the most dangerous pathogens that can be transmitted with blood. Previously, a composition consisting of fullerene layer applied on silica gel particles was shown to inactivate influenza virus up to complete loss of infectivity. METHODS: In the present study the unit has been developed with source of irradiation whose spectrum is appropriate for solid-phase fullerene. The ability of the unit to inactivate the enveloped influenza virus in protein fraction of donor blood has been studied. RESULTS: It was shown that at optimized conditions complete inactivation of enveloped virus of extremely high initial titer (7.0-9.5 log 10 EID 50/0.2 mL) in the solution of albumin was achieved after as short time as 30 min of irradiation. This process did not affect the oxidative metabolism of neutrophils and membranes of erythrocytes evaluated by NBT reduction test and morphological analysis of erythrocytes, respectively. CONCLUSION: The data obtained suggests that the method described can be recommended for further development and optimization of the procedure of inactivation of viruses in the preparations of the plasma of donor blood.


Subject(s)
Blood Proteins/drug effects , Blood Proteins/radiation effects , Fullerenes/administration & dosage , Influenza A virus/drug effects , Influenza A virus/physiology , Virus Inactivation/drug effects , Virus Inactivation/radiation effects , Animals , Dogs , Fullerenes/chemistry , Influenza A virus/radiation effects , Madin Darby Canine Kidney Cells , Phase Transition , Photochemotherapy/methods
19.
Vopr Virusol ; 59(5): 31-8, 2014.
Article in Russian | MEDLINE | ID: mdl-25895209

ABSTRACT

Influenza virus is a leading causing factor of infectious respiratory human pathology. The search and development of novel anti-influenza drugs with a wide spectrum of activity is an important goal for medical science. In addition to specific anti-viral activity of the compound, its way of application is of great importance. In this work, we present the results of the study of the activity of a combination of glutamyl-tryptophan with glycirrhyzic acid (GTGA) against oseltamivir-resistant strain of the virus A/Vladivostok/2/09 (H1N1) at per os application on the model of the lethal influenza infection in white mice. The application of the GTGA was shown to decrease the specific mortality of animals (index of protection 43-50%), to increase the mean day of death to 2.5-3.9 days, and to reduce the infectious titer of the virus in the lung tissue to 1.5-1.9 Ig EID50/20 mg. The corresponding values for the reference compound oseltamivir were 14-25%, 1.1-1.9 days and 0.7 Ig EID50/20 mg, respectively, depending on the dose of the virus. The use of the GTGA also led to a reliable increase of the titers of interferon in the blood from 44.3 to 66.3 ME/mL. Morphological analysis revealed that GTGA lead to normalization of the structure of the lung tissue restricting the level of the cytodestruction and inflammation. The results obtained in this work allow the combination studied to be suggested as a promising anti-influenza drug that is active against the drug-resistant virus strains and can be applied orally.


Subject(s)
Antiviral Agents/pharmacology , Dipeptides/pharmacology , Glycyrrhizic Acid/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Lung/drug effects , Orthomyxoviridae Infections/drug therapy , Administration, Oral , Animals , Drug Combinations , Drug Resistance, Viral , Female , Influenza A Virus, H1N1 Subtype/growth & development , Lung/pathology , Lung/virology , Mice , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Oseltamivir/pharmacology , Survival Analysis , Viral Load/drug effects
20.
Antibiot Khimioter ; 58(1-2): 36-48, 2013.
Article in Russian | MEDLINE | ID: mdl-24640143

ABSTRACT

The problem of prophylaxis and therapy of influenza infections remains one of the priority goals for medical science and practical health care. The review includes the discussion of antiviral activity of Deitiforine, a Russian chemotherapeutic. The data on the toxicity and the specific activity spectrum in cell cultures, chicken embryos and laboratory animals are presented. The problem of the influenza viruses resistance to cage compounds and in particular to rimantadine and Deitiforine is also discussed.


Subject(s)
Antiviral Agents/pharmacology , Drug Resistance, Viral/drug effects , Influenza A virus , Influenza, Human/drug therapy , Animals , Cell Culture Techniques , Chick Embryo , Humans , Organic Chemicals/pharmacology
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