234 results on '"Galegov GA"'
Search Results
2. THE MECHANISM OF STIMFORTE ACTION ON HERPESVIRUS INFECTION
- Author
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S. S. Grigorian, E. I. Isaeva, A. A. Terentyev, A. A. Balakina, V. L. Andronova, D. G. Mal’dov, Galegov Ga, and A. V. Ilyichev
- Subjects
Gene Expression Regulation, Viral ,0301 basic medicine ,Drug ,medicine.medical_treatment ,media_common.quotation_subject ,Herpesvirus 1, Human ,Biology ,Virus Replication ,medicine.disease_cause ,Granzymes ,Microbiology ,Interferon-gamma ,Mice ,03 medical and health sciences ,Interferon ,Virology ,medicine ,Animals ,Humans ,Organic Chemicals ,Lung ,media_common ,Innate immune system ,Protease ,Brain ,Herpesviridae Infections ,Interferon-beta ,General Medicine ,030112 virology ,Killer Cells, Natural ,Granzyme B ,Infectious Diseases ,Herpes simplex virus ,medicine.drug - Abstract
Increased protease activity and a significant amount of granzyme B were observed in in organs of mice infected with acute herpes simplex virus HSV-1 with the introduction of Stimforte (100 or 250 µg/mouse). Thus, this drug activates killer cells, which play an extremely important role in the suppression of HSV-1 infection. Although the administration of Stimforte (100 μg/mouse) to intact mice results in the activation of IFN-β production and does not activate the production of IFN-λ, Stimforte administration to animals infected with HSV-1 reduces production of IFN-β in serum, brain and lungs, whereas the production of IFN-λ considerably increases as the result of administration of 100 μg/mouse of Stimforte.
- Published
- 2018
3. Chemoenzymatic Synthesis of Modified 2′-Deoxy-2′-fluoro-β-d-arabinofuranosyl Benzimidazoles and Evaluation of Their Activity Against Herpes Simplex Virus Type 1
- Author
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Irina D. Konstantinova, Valery N. Charushin, I. V. Fateev, Galegov Ga, Anatoly I. Miroshnikov, Alexander S. Paramonov, Maria I. Kharitonova, Svetlana K. Kotovskaya, Alexei L. Kaushin, Valeria L. Аndronova, Мaria Ya. Berzina, and Konstantin V. Аntonov
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Purine ,chemistry.chemical_classification ,Benzimidazole ,Glycosylation ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Purine nucleoside phosphorylase ,medicine.disease_cause ,01 natural sciences ,Catalysis ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Herpes simplex virus ,Enzyme ,chemistry ,medicine ,Vero cell ,Nucleoside - Abstract
1-(2′-Deoxy-2′-fluoro-β- d -arabinofuranosyl)benzimidazoles containing 4,6-difluoro-, 4,5,6-trifluoro-, 5-fluoro-6-methoxy-, and 5-methoxy-4,6-difluorobenzimidazole fragments were synthesized by using purine nucleoside phosphorylase-catalyzed chemoenzymatic approach. As expected, enzymatic synthesis of nucleosides proceeds in lower yields of target compounds in comparison with the synthesis of ribo- and 2′-deoxyribobenzimidazoles (40–55% vs 60–90%). The compounds obtained were tested against the herpes simplex virus type 1, by using the Vero E6 cells. 5-Methoxy-4,6-difluoro-1-β- d -(2′-deoxy-2′-fluoroarabinofuranosyl)benzimidazole did not show any antiviral activity, when used in nontoxic concentration. All other nucleosides proved to exhibit a selective antiherpes activity. In contrast, it was shown that benzimidazole-β- d -arabinofuranosides of both di- and trisubstituted derivatives, having substituents in positions 4–6 of the benzene ring, as well as unsubstituted compounds, cannot be synthesized by enzymatic transglycosylation. 1-(β- d -Arabinofuranosyl)benzimidazole was obtained through glycosylation of N -trimethylsilylbenzimidazole with 1-chloro-2,3,5- O -methoxymethyl- d -arabinose. The behavior of this compound, as inhibitor of purine nucleoside phosphorylase (PNP) E. сoli , was investigated . 1-(β- d -Arabinofuranosyl)benzimidazole was found to belong to a mixed type of inhibitors of PNP. This fact explains why all attempts to perform enzymatic arabinosylation of 4,6-di-, 5,6-di-, and 4,5,6-trisubstituted benzimidazoles failed.
- Published
- 2016
4. Enzymatic synthesis of novel purine nucleosides bearing a chiral benzoxazine fragment
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Roman S. Esipov, Tatyana I. Muravyova, Alexander S. Paramonov, Inessa S. Muzyka, Galina L. Levit, Irina D. Konstantinova, Barbara Z. Eletskaya, Valeria L. Andronova, Alexei L. Kayushin, Valery N. Charushin, Victor P. Krasnov, M. A. Kostromina, Anatoly I. Miroshnikov, Galegov Ga, and Dmitry A. Gruzdev
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Purine ,Deoxyribonucleosides ,Stereochemistry ,Adenosine Deaminase ,Cell Survival ,Deamination ,Herpesvirus 1, Human ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,Antiviral Agents ,Nucleobase ,chemistry.chemical_compound ,Adenosine deaminase ,Drug Discovery ,Chlorocebus aethiops ,Drug Resistance, Viral ,medicine ,Escherichia coli ,Animals ,Humans ,Vero Cells ,Pharmacology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Escherichia coli Proteins ,Organic Chemistry ,Stereoisomerism ,Purine Nucleosides ,0104 chemical sciences ,Benzoxazines ,010404 medicinal & biomolecular chemistry ,Enzyme ,chemistry ,biology.protein ,Molecular Medicine ,Nucleoside - Abstract
A series of ribo- and deoxyribonucleosides bearing 2-aminopurine as a nucleobase with 7,8-difluoro- 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (conjugated directly or through an aminohexanoyl spacer) was synthesized using an enzymatic transglycosylation reaction. Nucleosides 3-6 were resistant to deamination under action of adenosine deaminase (ADA) Escherichia coli and ADA from calf intestine. The antiviral activity of the modified nucleosides was evaluated against herpes simplex virus type 1 (HSV-1, strain L2). It has been shown that at sub-toxic concentrations, nucleoside (S)-4-[2-amino-9-(β-D-ribofuranosyl)-purin-6-yl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine exhibit significant antiviral activity (SI > 32) on the model of HSV-1 in vitro, including an acyclovir-resistant virus strain (HSV-1, strain L2/R).
- Published
- 2018
5. Interaction of a dimeric distamycin analog with poly(dA)poly(dT), poly[d(A–T)]poly[d(A–T)], and duplex O23 at the origin of replication of the herpes simplex virus
- Author
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Galegov Ga, E. D. Moiseeva, S. L. Grokhovsky, A. N. Surovaya, Bazhulina Np, G. V. Gursky, V. L. Andronova, and S. Yu. Lepehina
- Subjects
0301 basic medicine ,Circular dichroism ,Chemistry ,Stereochemistry ,Biophysics ,Origin of replication ,03 medical and health sciences ,030104 developmental biology ,Ultraviolet visible spectroscopy ,Duplex (building) ,Polyamide ,Molecule ,Binding site ,Selectivity - Abstract
The binding of a dimeric distamycin analog (Pt–bis–Dst) to poly[d(A–T)]poly[d(A–T)], poly(dA)poly(dT), and duplex O23 with the sequence 5’-GCCAATATATATATATTATTAGG-3’, which occurs at the origin of replication (OriS) of the herpes simplex virus, was studied via UV and CD spectroscopy. The synthetic polyamide differs from the natural antibiotic in having two distamycin moieties that are linked via a glycine cis-diamino platinum group. The Pt–bis–Dst binding to poly[d(A–T)]poly[d(A–T)] and poly(dA)poly(dT) reached saturation at approximately one ligand molecule per eight bp. As the ligand–base pair ratio further increased, the maximum wavelength band tended to shift toward longer wavelengths in the CD spectra of complexes with poly[d(A–T)]poly[d(A–T)] and a shoulder appeared in the 290–310 nm spectral region that was absent from the CD spectra of complexes with lower ligand coverages. At higher ligand–oligonucleotide molar ratios, Pt–bis–Dst could bind to poly[d(A–T)]poly[d(A–T)] in the form of hairpins or associations that result from interactions between the distamycin moieties of two neighbor Pt–bis–Dst molecules. The structures of the complexes were stabilized by interactions between the pirrolcarboxamide moieties of two Pt–bis–Dst molecules absorbed on adjacent overlapping binding sites. The interactions could also be responsible for the concentration-dependent spectral changes that were observed during the formation of a complex between Pt–bis–Dst and poly[d(A–T)]poly[d(A–T)]. Spectral changes were almost absent in the case of Pt–bis–Dst binding to poly(dA)poly(dT). The binding of Pt–bis–Dst to duplex O23 reached saturation at two ligand molecules per duplex, which contained a cluster of 18 AT pairs. At higher molar-concentration ratios, duplex CD spectra underwent changes similar to those that were observed for Pt–bis–Dst binding to poly[d(A–T)]poly[d(A–T)]. Testing Pt–bis–Dst for antiviral activity identified 1.5 μg/mL as a concentration that halved the cytopathic effect of the herpes simplex virus on Vero E6 cells; the selectivity index of antiviral action was 65; cytotoxicity was relatively low. The Pt–bis–Dst concentration that caused the death of approximately half of the cells was estimated at 100 μg/mL.
- Published
- 2016
6. Effect of dimeric netropsin analogue 15Lys-bis-Nt and acyclovir on the reproduction of herpes simplex virus type 1. The search for variants of herpes virus with drug resistance to 15Lys-bis-Nt and acyclovir
- Author
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Galegov Ga, Valeria L. Andronova, A. N. Surovaya, S. L. Grokhovsky, and G. V. Gursky
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Molecular Sequence Data ,Biophysics ,Acyclovir ,Herpesvirus 1, Human ,Drug resistance ,Biology ,Virus Replication ,medicine.disease_cause ,Antiviral Agents ,Biochemistry ,chemistry.chemical_compound ,Herpes virus ,Chlorocebus aethiops ,Drug Resistance, Viral ,medicine ,Animals ,Drug Interactions ,Amino Acid Sequence ,Vero Cells ,Dose-Response Relationship, Drug ,Molecular Structure ,Netropsin ,General Chemistry ,General Medicine ,Virology ,Herpes simplex virus ,Viral replication ,chemistry ,Vero cell ,Dimerization - Published
- 2015
7. New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1
- Author
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Maria I. Kharitonova, Svetlana K. Kotovskaya, Alexandra O. Denisova, Irina D. Konstantinova, Valeria L. Andronova, Alexei L. Kayushin, Valery N. Charushin, Anatoly I. Miroshnikov, and Galegov Ga
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Foscarnet ,viruses ,Clinical Biochemistry ,Herpes infections ,Organophosphonates ,Pharmaceutical Science ,Acyclovir ,Herpesvirus 1, Human ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,Antiviral Agents ,Virus ,chemistry.chemical_compound ,Cytosine ,Drug Discovery ,Drug Resistance, Viral ,medicine ,Humans ,Molecular Biology ,chemistry.chemical_classification ,2-aminobenzimidazole ,010405 organic chemistry ,Organic Chemistry ,virus diseases ,Nucleosides ,biochemical phenomena, metabolism, and nutrition ,Riboside ,Virology ,0104 chemical sciences ,Enzyme ,Herpes simplex virus ,chemistry ,Molecular Medicine ,Benzimidazoles ,Cidofovir ,medicine.drug - Abstract
Using the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient.
- Published
- 2017
8. Молекулярно-генетический анализ генов ДНК-полимеразы и тимидинкиназы популяции вируса герпеса простого первого типа методом массивного параллельного секвенирования
- Author
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Skoblov IuS, V. L. Andronova, A. A. Gus’kova, D. A. Zubtsov, Skoblov MIu, Alexander Lavrov, Gol'dshteĭn Dv, and Galegov Ga
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education.field_of_study ,biology ,DNA polymerase ,viruses ,Population ,General Medicine ,medicine.disease_cause ,Molecular biology ,Virus ,law.invention ,chemistry.chemical_compound ,Herpes simplex virus ,chemistry ,law ,Vero cell ,medicine ,biology.protein ,education ,Gene ,DNA ,Polymerase chain reaction - Abstract
It was determined the ratio of viral DNA and DNA from Vero cells using the polymerase chain reaction in real time in Vero cell lysate, infected with L2 strain of the herpes simplex virus type 1. Copy number of the virus reached a maximum after 24 hours of incubation of infection. Total DNA was isolated and sequenced using NGS technology by Ion Torrent device. Nucleotide sequences of the thymidine kinase gene (UL23) and DNA polymerase (UL30) were determined for a population of HSV-1 strain L2. Comparison of the primary structure of these genes with the corresponding nucleotide sequences of known strains of HSV-1 KOS and 17 was conducted. Differences in the structure of genes UL23 and UL30 between strain L2 and reference strains KOS and 17 are not important, because changes are found in non-conservative regions.
- Published
- 2013
9. Phosphoramidate derivatives of acyclovir: Synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro
- Author
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N. F. Zakirova, Maxim V. Jasko, Vladimir S. Prassolov, Galegov Ga, Valeria L. Andronova, Sergey N. Kochetkov, Alexander V. Shipitsyn, and M M Prokofjeva
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Guanine ,viruses ,Clinical Biochemistry ,Acyclovir ,Pharmaceutical Science ,HIV Infections ,Herpesvirus 1, Human ,Virus Replication ,Antiviral Agents ,Biochemistry ,chemistry.chemical_compound ,Chlorocebus aethiops ,Drug Discovery ,Animals ,Humans ,Cytotoxicity ,Vero Cells ,Molecular Biology ,Strain (chemistry) ,Organic Chemistry ,virus diseases ,Herpes Simplex ,Phosphoramidate ,Virology ,In vitro ,HEK293 Cells ,Viral replication ,chemistry ,HIV-1 ,Vero cell ,Molecular Medicine ,Chemical stability - Abstract
The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity.
- Published
- 2012
10. Inhibition of herpes simplex virus helicase UL9 by netropsin derivatives and antiviral activities of bis-netropsins
- Author
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S. L. Grokhovsky, A. M. Nikitin, Bazhulina Np, Galegov Ga, M. V. Golovkin, V. L. Andronova, A. N. Surovaya, Y.G. Gursky, V. S. Arkhipova, and G. V. Gursky
- Subjects
biology ,Oligonucleotide ,Base pair ,viruses ,Biophysics ,DNA replication ,Helicase ,RNA Helicase A ,DNA-binding protein ,Molecular biology ,chemistry.chemical_compound ,chemistry ,Netropsin ,biology.protein ,DNA - Abstract
Data obtained show that antiviral activities of bis-linked netropsin derivatives are targeted by specific complexes formed by helicase UL9 of herpes simplex virus type 1 with viral DNA replication origins, represented by two OriS sites and one OriL site. According to the results of footprinting studies bis-netropsins get bound selectively to an A+T-cluster which separates interaction sites I and II for helicase UL9 in OriS. Upon binding to DNA bis-netropsins stabilize a structure of the A+T-cluster and inhibit thermal fluctuation-induced opening of AT- base pairs which is needed for local unwinding of DNA by helicase UL9. Kinetics of ATP-dependent DNA unwinding in the presence and absence of Pt-bis-netropsin are studied by measuring the efficiency of Forster resonance energy transfer (FRET) between the fluorescent probes attached covalently to 3?- and 5?-ends of the oligonucleotides in the minimal OriS duplex. Pt-bis-netropsin and related molecules inhibit unwinding of OriS duplex by helicase UL9. Pt-bis-netropsin is also able to reduce the rate of unwinding of the AT- rich hairpin formed by the upper strand in the minimal OriS duplex. The antiviral activities and toxicity of bis-linked netropsin derivatives are studied in cell cultured experiments and experiments with animals infected by herpes virus.
- Published
- 2012
11. Enzymatic activity of thymidine kinases of a herpes simplex virus strains resistant to acyclovir H-phosphonates
- Author
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Yu. S. Skoblov, Sergey N. Kochetkov, V.L. Andronova, Galegov Ga, M. Yu. Skoblov, and A. A. Gus’kova
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chemistry.chemical_classification ,Kinase ,viruses ,Organic Chemistry ,Mutant ,medicine.disease_cause ,Biochemistry ,Virology ,chemistry.chemical_compound ,Herpes simplex virus ,Enzyme ,chemistry ,Thymidine kinase ,medicine ,Phosphorylation ,Bioorganic chemistry ,Thymidine - Abstract
Some cloned laboratory mutant strains of herpes simplex virus type I resistant to acyclovir H-phosphonate were studied. As was shown for all the clones, the mutations augmented the susceptibility to cidifovir. Thymidine kinase of the mutant viruses partially retained the capacity to phosphorylate thymidine, but lost the capacity to phosphorylate BVDU.
- Published
- 2011
12. 1,2,4-Triazoloazine derivatives as a new type of herpes simplex virus inhibitors
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A. N. Korovina, Inna L. Karpenko, T. S. Shestakova, Galegov Ga, V.L. Andronova, Vladimir L. Rusinov, Oleg N. Chupakhin, Anastasia L. Khandazhinskaya, Marina K. Kukhanova, Sergey L. Deev, Maxim V. Yasko, and E. N. Ulomskii
- Subjects
Models, Molecular ,Cell Survival ,DNA polymerase ,DNA-Directed DNA Polymerase ,Herpesvirus 1, Human ,Virus Replication ,medicine.disease_cause ,Antiviral Agents ,Biochemistry ,Cell Line ,Single-stranded binding protein ,chemistry.chemical_compound ,Polyphosphates ,Chlorocebus aethiops ,Drug Discovery ,medicine ,Animals ,Humans ,Vero Cells ,Molecular Biology ,Polymerase ,Nucleic Acid Synthesis Inhibitors ,biology ,DNA synthesis ,Triazines ,Organic Chemistry ,Herpes Simplex ,Triazoles ,Molecular biology ,Herpes simplex virus ,chemistry ,Viral replication ,biology.protein ,Nucleic acid ,DNA - Abstract
A new class of inhibitors of herpes simplex virus replication was found. The compounds under study are derived from condensed 1,2,4-triazolo[5,1-c][1,2,4]triazines and 1,2,4-triazolo[1,5-a]pyrimidines, structural analogues of natural nucleic bases. Antiherpetic activity and cytotoxicity of the compounds were studied. The corresponding triphosphates of several active compounds were prepared and tested as inhibitors of DNA synthesis catalyzed by herpes simplex virus polymerase. The potential mechanism of their action is blocking of DNA dependent DNA polymerase, a key enzyme of viral replication.
- Published
- 2010
13. Temperature-induced conformational transitions of the glucanotransferase Bgl2p isolated from Saccharomyces cerevisiae cell walls
- Author
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M Iu Skoblov, A. A. Gus’kova, Galegov Ga, Marina K. Kukhanova, Sergey N. Kochetkov, V. L. Andronova, Iu S Skoblov, and A. N. Korovina
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biology ,DNA polymerase ,viruses ,Point mutation ,Biophysics ,Drug resistance ,medicine.disease_cause ,Virology ,Molecular biology ,Herpes simplex virus ,Structural Biology ,Cell culture ,Thymidine kinase ,biology.protein ,Homologous chromosome ,medicine ,Gene - Abstract
The primary structures of DNA-polymerase (ul30) and thymidine kinase (ul23) genes from several herpes simplex virus type 1 (HSV-1) clinical isolates which differed in sensitivity for a number of antiherpetic drugs were determined and compared with those for two laboratory HSV-1 strains one of which was ACV-sensitive (L2), while the another was resistant (L2) to ACV. The phylogenetic analysis of the sequences showed that conserved regions of ul30 gene of HSV-1 clinical isolates and L2 strain were homologous with the exception of point mutations and degenerated substitutions. Several new mutations in the HSV-1 DNA-polymerase and thymidine kinase functional domains were established and identified as the substitutions associated with the strain-resistance to ACV and other drugs.
- Published
- 2010
14. Complex of the herpes simplex virus initiator protein UL9 with DNA as a platform for the design of a new type of antiviral drugs
- Author
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V.L. Andronova, V. S. Arkhipova, Galegov Ga, Y.G. Gursky, S. L. Grokhovsky, A. N. Surovaya, G. V. Gursky, and Bazhulina Np
- Subjects
biology ,Base pair ,viruses ,Biophysics ,Helicase ,Protein dimer ,Plasma protein binding ,biochemical phenomena, metabolism, and nutrition ,Origin of replication ,Molecular biology ,Single-stranded binding protein ,chemistry.chemical_compound ,chemistry ,biology.protein ,Binding site ,DNA - Abstract
The protein binding to the origin of replication of the herpes simplex virus type 1 is DNA helicase encoded by the UL9 gene of the herpes virus. The protein specifically binds to two binding sites in the viral DNA replication origins OriS or OriL. In order to determine the role of the UL9 protein in the initiation of replication and find efficient inhibitors of the UL9 activity, we have synthesized a recombinant UL9 protein expressed in E. coli cells. It was found that the recombinant UL9 protein binds to Boxes I and II in OriS and possesses DNA helicase and ATPase activities. In the complex with a fluorescent analog of ATP, two molecules of the ATP analog bind to one protein dimer molecule. It was also found that the UL9 protein in the dimer form can bind simultaneously to two DNA fragments, each containing specific binding sites for the protein. The interaction of the recombinant UL9 protein with the 63-mer double- and single-stranded oligonucleotides OriS and OriS*, which correspond to the origin of replication of herpes simplex virus, has been investigated. From the titrations of OriS and OriS* with ethidium bromide in the presence and absence of the UL9 protein, the equilibrium affinity constants of the protein binding to OriS and OriS* have been determined. A DNase I footprinting study showed that bis-netropsins exhibit preference for binding to the AT cluster in the origin of replication OriS and inhibit the fluctuation opening of AT base pairs in the AT cluster. The drugs also prevent formation of an intermediate conformation of OriS* that involves a disordered tail at the 3′ end and stable Box I-Box III hairpin to which the UL9 helicase selectively binds. The stabilization by bis-netropsins of the AT-rich hairpin at its 3′ end can inhibit the helicase activity. It was concluded that the antiviral activity of bis-netropsins may be associated with the inhibitory effects of bis-netropsins on these two stages of the reaction catalyzed by helicase UL9.
- Published
- 2010
15. DNA-binding and antiviral activity of bis-netropsins containing clusters of lysine residues in the N-terminal region
- Author
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G. V. Gurskii, Galegov Ga, A. N. Surovaya, V.L. Andronova, and S. L. Grokhovskii
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DNA Replication ,Lysine ,Biophysics ,Netropsin ,General Chemistry ,General Medicine ,Biology ,Virus Replication ,Antiviral Agents ,Biochemistry ,chemistry.chemical_compound ,Terminal (electronics) ,chemistry ,Chlorocebus aethiops ,DNA, Viral ,Animals ,Vero Cells ,DNA - Published
- 2004
16. Analysis of Antiviral Properties of Hexoral In Vitro against Some Viruses that Cause Acute Respiratory Infections and Herpes
- Author
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Galegov Ga, A. G. Botikov, P. G. Deryabin, and V. A. Andronova
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0301 basic medicine ,viruses ,Virulence ,Hexetidine ,medicine.disease_cause ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dogs ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Respiratory system ,Respiratory Tract Infections ,Vero Cells ,Respiratory tract infections ,Influenza A Virus, H5N1 Subtype ,Viral culture ,business.industry ,General Medicine ,Virology ,Influenza A virus subtype H5N1 ,030104 developmental biology ,Herpes simplex virus ,chemistry ,business ,030217 neurology & neurosurgery - Abstract
Antiviral properties of Hexoral (0.1% solution and 0.2% aerosol for local application) and its constituent hexetidine against viruses causing human respiratory tract infections and herpes virus were studied in vitro. It was found that non-cytotoxic concentrations of hexetidine (alone and as a component of Hexoral) attenuated infectious properties of highly virulent influenza virus A/H5N1, pandemic influenza virus A/H1N1pdm, respiratory syncytial virus, and herpes simplex virus type 1 after a short-term exposure (30 sec) by 100 or more times. It was found that hexidine mostly contributes to the virucidal effect of Hexoral.
- Published
- 2014
17. [Untitled]
- Author
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A. N. Surovaya, G. V. Gurskii, Galegov Ga, V.L. Andronova, and S. L. Grokhovskii
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chemistry.chemical_compound ,chemistry ,Netropsin ,Stereochemistry ,Biophysics ,General Chemistry ,General Medicine ,Biochemistry - Published
- 2001
18. The combination of ribavirin and ozeltamivir effectively inhibits reproduction of influenza A virus resistant to rimantadine (amantadine) in vitro and in vivo
- Author
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Galegov Ga, P. G. Deryabin, Inessa S. Muzyka, Anatoly I. Miroshnikov, Irina D. Konstantinova, and L'vov Dk
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Oseltamivir ,Rimantadine ,Biophysics ,medicine.disease_cause ,Virus Replication ,Biochemistry ,Antiviral Agents ,Madin Darby Canine Kidney Cells ,chemistry.chemical_compound ,Mice ,Zanamivir ,Dogs ,Orthomyxoviridae Infections ,In vivo ,Drug Resistance, Viral ,Ribavirin ,Influenza A virus ,Amantadine ,Medicine ,Animals ,business.industry ,General Chemistry ,General Medicine ,Virology ,In vitro ,Drug Combinations ,chemistry ,business ,medicine.drug - Published
- 2013
19. Comparative study of reproduction of sindbis virus sensitive and resistant to adamantane derivatives
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V. L. Andronova and Galegov Ga
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Sindbis virus ,Strain (chemistry) ,viruses ,media_common.quotation_subject ,RNA ,General Medicine ,Biology ,biology.organism_classification ,Virology ,General Biochemistry, Genetics and Molecular Biology ,Resistant virus ,Adamantane derivatives ,Viral replication ,Reproduction ,Incubation ,media_common - Abstract
The sensitivity of Sindbis virus gradually decreases during serial passages in the presence of 1-adamantane carbonic acid amide. After 4 passages, viral reproduction was not suppressed even by subtoxic concentrations of the inhibitor. Sensitive Sindbis strain principally differed from the resistant one: the latency of reproduction of resistant virus was 2 h longer than that of the sensitive strain. Cells infected with the sensitive and resistant strains of Sindbis virus contained the major structural proteins (C, E1+E2), their precursors pE2, p130, p90, and p78 protein, which probably represent a nonstructural virus-specific protein nsP3. The synthesis of virus-specific polypeptides and RNA of resistant variant is resistant to the inhibitor during incubation.
- Published
- 2000
20. Combined antiherpetic effect of complex preparation 'Viferon® — eye drops' and modified nucleosides
- Author
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Galegov Ga, V. V. Malinovskaya, V. L. Andronova, and E. N. Vyzhlova
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Drug ,viruses ,media_common.quotation_subject ,Acyclovir ,Herpesvirus 1, Human ,Interferon alpha-2 ,Biology ,Pharmacology ,medicine.disease_cause ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,Dosage form ,law.invention ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Species Specificity ,law ,Idoxuridine ,Chlorocebus aethiops ,Ribavirin ,medicine ,Animals ,Ganciclovir ,Vero Cells ,media_common ,Dose-Response Relationship, Drug ,Interferon-alpha ,Nucleosides ,Combination chemotherapy ,General Medicine ,Recombinant Proteins ,In vitro ,Herpes simplex virus ,chemistry ,Biochemistry ,Cell culture ,Recombinant DNA ,Ophthalmic Solutions ,Vidarabine - Abstract
Ready dosage form (eye drops) prepared on the basis of recombinant alpha2-IFN exhibits high activity towards herpes simplex type 1 virus in vitro. Systematic study of the antiherpesvirus effect of this drug in combination with modified nucleosides showed an inhibitory effect of the synergic type. Combination of IFN preparation with some nucleosides, including ribavirin, proved to be highly effective towards drug-resistant herpes virus.
- Published
- 2006
21. Synergic antiherpetic effect of para-aminobenzoic acid and modified nucleosides
- Author
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Stroeva Og, Leont'eva Na, Akberova Si, and Galegov Ga
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viruses ,General Medicine ,Biology ,medicine.disease_cause ,Virology ,Modified nucleosides ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Microbiology ,Herpes simplex virus ,medicine ,Vero cell ,Combined therapy ,PARA-AMINOBENZOIC ACID - Abstract
New results of combined therapy of herpetic infection in Vero cells infected with herpes simplex type I virus resistant to acyclovir (acycloguanosine, Zovirax) are presented. Paraaminobenzoic acid stimulates antiherpetic effects of acycloguanosine, 5-(2-bromovinyl)-2′-deoxyuridine and adenine 9-β-d-arabinofuranoside. para-aminobenzoic acid alone is incapable of suppressing type I herpes simplex virus reproduction in cell culture. Modified nucleosides combined with it exert a higher selective antiherpetic effect. Para-aminobenzoic acid is capable of inactivating herpes viruses in culture medium.
- Published
- 1997
22. Combined Effect of Basic Antiherpetic Drugs with a New Inhibitor of the Terminase Complex of Herpes Simplex Virus Type 1 in Vero Cell Cultures.
- Author
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Andronova VL, Galegov GA, Vozdvizhenskaya OA, Levit GL, Krasnov VP, and Charushin VN
- Subjects
- Vero Cells, Chlorocebus aethiops, Animals, Ganciclovir pharmacology, Foscarnet pharmacology, Guanine analogs & derivatives, Guanine pharmacology, Cidofovir pharmacology, Humans, Bromodeoxyuridine analogs & derivatives, Antiviral Agents pharmacology, Herpesvirus 1, Human drug effects, Herpesvirus 1, Human physiology, Endodeoxyribonucleases metabolism, Endodeoxyribonucleases antagonists & inhibitors, Acyclovir pharmacology
- Abstract
Carriers of herpes simplex virus type 1 (HSV-1) account for more than 90% of the global population. Infection manifests itself in the formation of blisters and ulcers on the face or genitals and can cause blindness, encephalitis, and generalized infection. All first- and second-line modern antiherpetic drugs selectively inhibit viral DNA polymerase. The purine-benzoxazine conjugate LAS-131 ((S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine), which we have described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits HSV-1 reproduction in vitro. Basically new results were for the first time obtained to characterize the combined effect on human herpesvirus infection for LAS-131 used in combination with practically significant antiviral compounds, including the nucleoside analogs acyclovir (ACV), penciclovir (PCV), ganciclovir (GCV), brivudine (BVdU), iododeoxyuridine (IdU), and adenine arabinoside (Ara-A); the nucleoside phosphonate analog cidofovir (CDV); and the pyrophosphate analog foscarnet (FOS). A cytopathic effect (CPE) inhibition assay showed that the drug concentration that inhibited the virus-induced CPE by 50% decreased by a factor of 2 (an additive effect, FOS) or more (a synergistic effect; ACV, PCV, GCV, IdU, BVdU, Ara-A, and CDV) when the drugs were used in combination with LAS-131. Nonpermissive conditions for HSV-1 reproduction were thus created at lower drug concentrations, opening up new real possibilities to control human herpesvirus infection., (© 2024. Pleiades Publishing, Ltd.)
- Published
- 2024
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23. Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase.
- Author
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Fateev IV, Sasmakov SA, Abdurakhmanov JM, Ziyaev AA, Khasanov SS, Eshboev FB, Ashirov ON, Frolova VD, Eletskaya BZ, Smirnova OS, Berzina MY, Arnautova AO, Abramchik YA, Kostromina MA, Kayushin AL, Antonov KV, Paramonov AS, Andronova VL, Galegov GA, Esipov RS, Azimova SS, Miroshnikov AI, and Konstantinova ID
- Subjects
- Thiones chemistry, Thiones pharmacology, Thiones chemical synthesis, Animals, Chlorocebus aethiops, Vero Cells, Triazoles chemistry, Triazoles pharmacology, Triazoles chemical synthesis, Purine-Nucleoside Phosphorylase metabolism, Purine-Nucleoside Phosphorylase antagonists & inhibitors, Antiviral Agents pharmacology, Antiviral Agents chemical synthesis, Antiviral Agents chemistry, Escherichia coli drug effects, Escherichia coli enzymology, Nucleosides chemistry, Nucleosides chemical synthesis, Nucleosides pharmacology
- Abstract
1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this study was to synthesize ribosides and deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex viruses. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for E. coli purine nucleoside phosphorylase. Of six prepared nucleosides, the riboside and deoxyriboside of 3-phenacylthio-1,2,4-triazole were obtained at good yields. The yields of the disubstituted 1,2,4-triazol-3-thiones were low due to the effect of bulky substituents at the C3 and C5 positions on the selectivity of enzymatic glycosylation for one particular nitrogen atom in the triazole ring. The results of cytotoxic and antiviral studies on acyclovir-sensitive wild-type strain HSV-1/L2(TK+) and acyclovir-resistant strain (HSV-1/L2/R
ACV ) in Vero E6 cell culture showed that the incorporation of a thiobutyl substituent into the C5 position of 3-phenyl-1,2,4-triazole results in a significant increase in the cytotoxicity of the base and antiviral activity. The highest antiviral activity was observed in the 3-phenacylthio-1-(β- D -ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-β- D -ribofuranosyl)-3-phenyl-1,2,4-triazole nucleosides, with their selectivity indexes being significantly higher than that of ribavirin. It was also found that with the increasing lipophilicity of the nucleosides, the activity and toxicity of the tested compounds increased.- Published
- 2024
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24. Large Subunit of the Human Herpes Simplex Virus Terminase as a Promising Target in Design of Anti-Herpesvirus Agents.
- Author
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Krasnov VP, Andronova VL, Belyavsky AV, Borisevich SS, Galegov GA, Kandarakov OF, Gruzdev DA, Vozdvizhenskaya OA, and Levit GL
- Subjects
- Humans, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Acyclovir pharmacology, DNA-Directed DNA Polymerase genetics, Drug Resistance, Viral, Herpes Simplex drug therapy, Herpesvirus 1, Human
- Abstract
Herpes simplex virus type 1 (HSV-1) is an extremely widespread pathogen characterized by recurrent infections. HSV-1 most commonly causes painful blisters or sores around the mouth or on the genitals, but it can also cause keratitis or, rarely, encephalitis. First-line and second-line antiviral drugs used to treat HSV infections, acyclovir and related compounds, as well as foscarnet and cidofovir, selectively inhibit herpesvirus DNA polymerase (DNA-pol). It has been previously found that ( S )-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2 H -[1,4]benzoxazine (compound 1 ) exhibits selective anti-herpesvirus activity against HSV-1 in cell culture, including acyclovir-resistant mutants, so we consider it as a lead compound. In this work, the selection of HSV-1 clones resistant to the lead compound was carried out. High-throughput sequencing of resistant clones and reference HSV-1/L
2 parent strain was performed to identify the genetic determinants of the virus's resistance to the lead compound. We identified a candidate mutation presumably associated with resistance to the virus, namely the T321I mutation in the UL15 gene encoding the large terminase subunit. Molecular modeling was used to evaluate the affinity and dynamics of the lead compound binding to the putative terminase binding site. The results obtained suggest that the lead compound, by binding to pUL15, affects the terminase complex. pUL15, which is directly involved in the processing and packaging of viral DNA, is one of the crucial components of the HSV terminase complex. The loss of its functional activity leads to disruption of the formation of mature virions, so it represents a promising drug target. The discovery of anti-herpesvirus agents that affect biotargets other than DNA polymerase will expand our possibilities of targeting HSV infections, including those resistant to baseline drugs.- Published
- 2023
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25. Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2 H -[1,4]benzoxazine and Evaluation of Their Antiviral Activity.
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Krasnov VP, Musiyak VV, Levit GL, Gruzdev DA, Andronova VL, Galegov GA, Orshanskaya IR, Sinegubova EO, Zarubaev VV, and Charushin VN
- Subjects
- Antiviral Agents chemistry, Benzoxazines chemistry, Purines, Pyrimidines pharmacology, Influenza A Virus, H1N1 Subtype, Influenza A virus
- Abstract
A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2 H -[1,4]benzoxazine and its ( S )-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by
1 H,19 F, and13 C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC. Antiviral evaluation of the synthesized compounds has shown that the replacement of purine with a pyrimidine fragment leads to a decrease in the anti-herpesvirus activity compared to the lead compound, purine conjugate. The studied compounds did not exhibit significant activity against influenza A (H1N1) virus.- Published
- 2022
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26. [Antiviral effect of novel purine conjugate LAS-131 against Herpes simplex virus type 1 (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1) in vitro].
- Author
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Andronova VL, Galegov GA, Musiyak VV, Vozdvizhenskaya OA, Levit GL, and Krasnov VP
- Subjects
- Acyclovir pharmacology, Antiviral Agents chemistry, Herpes Simplex pathology, Herpes Simplex virology, Herpesvirus 1, Human pathogenicity, Humans, Purines chemistry, Purines pharmacology, Antiviral Agents pharmacology, Herpes Simplex drug therapy, Herpesvirus 1, Human drug effects, Virus Replication drug effects
- Abstract
Introduction: Herpes simplex viruses type 1 (HSV-1) are extremely widespread throughout the world and, similar to other herpesviruses, establish lifelong persistent infection in the host. Reactivating sporadically, HSV-1 elicits recurrences in both immunocompetent and immunocompromised individuals and can cause serious diseases (blindness, encephalitis, generalized infections). The currently available antiherpetic drugs that aimed mainly at suppressing replication of viral DNA are not always effective enough, for example, due to the development of drug resistance. As we showed earlier the newly discovered compound LAS-131 exhibits the strong and highly selective inhibitory activity against HSV‑1, including strain resistant to acyclovir (selective index, SI = 63). The presence of LAS-131 at a concentration of 20 μg/ml leads to a decrease in the titer of HSV-1 (strain L2) by 4 lg in a one round of HSV-1 replication., Material and Methods: To establish the step(s) of the virus life cycle that is sensitive to the action of LAS-131, we have applied a widely used approach, that made it possible to determine how long the addition of a compound can be postponed before it loses its antiviral activity (time-of-addition assay), and to compare this indicator with the crucial time of application of inhibitors with a well-known mechanism of action (in cell culture)., Results: It has been shown for the first time that LAS-131 retains a pronounced antiviral effect when introduced into the experimental system no later than 9 hours post-infection (p.i.). However, LAS-131 does not affect the release of HSV-1 from the cell., Discussion: Together with published data on the termination of the synthesis of viral DNA 9-12 h after the adsorption in a cell culture infected with HSV with a high multiplicity (≥1 PFU/cell), our results suggest that LAS-131 interferes the life cycle of HSV-1 during synthesis of viral DNA. Further studies of the mechanism of action are necessary to establish definitely the biological target for this compound,.
- Published
- 2021
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27. The Mechanism of the Stimforte Effect on the Activation of Target Cell Defense against Viral Infection.
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Mal'dov DG, Deryabin PG, Grigoryan SS, Mishin DV, Andronova VL, Isaeva EI, Galegov GA, and Ilichev AV
- Subjects
- Acetylmuramyl-Alanyl-Isoglutamine pharmacology, Adjuvants, Immunologic administration & dosage, Adjuvants, Immunologic pharmacology, Animals, Antiviral Agents administration & dosage, Cell Survival drug effects, Chlorocebus aethiops, Dose-Response Relationship, Drug, Hepacivirus drug effects, Hepacivirus physiology, Hepatitis C immunology, Interferons metabolism, Lipopolysaccharides administration & dosage, Lipopolysaccharides pharmacology, Nod2 Signaling Adaptor Protein metabolism, Organic Chemicals administration & dosage, Toll-Like Receptor 4 metabolism, Vero Cells, Virus Replication drug effects, Antiviral Agents pharmacology, Hepatitis C drug therapy, Organic Chemicals pharmacology
- Abstract
Stimforte in a wide range of concentrations (15-225 µg/mL) totally inhibits the cytopathic activity of hepatitis C virus (HCV) in the Vero-V cell culture. Interferons (IFN) play the most important role in the suppression of infection when the drug is introduced into the culture before the infection. When Stimforte is introduced after the infection, the mechanism of action seems to be different. The activators of IFN production are mainly (or exclusively) the ligands of receptor complexes TLR-4 and NOD-2 contained in the drug. The action of these substances is probably synergistic, similar to the action of LPS and MDP in Vero-V cells.
- Published
- 2020
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28. Enzymatic synthesis of novel purine nucleosides bearing a chiral benzoxazine fragment.
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Eletskaya BZ, Gruzdev DA, Krasnov VP, Levit GL, Kostromina MA, Paramonov AS, Kayushin AL, Muzyka IS, Muravyova TI, Esipov RS, Andronova VL, Galegov GA, Charushin VN, Miroshnikov AI, and Konstantinova ID
- Subjects
- Animals, Antiviral Agents chemistry, Antiviral Agents pharmacology, Cell Survival drug effects, Chlorocebus aethiops, Drug Resistance, Viral drug effects, Escherichia coli enzymology, Escherichia coli Proteins metabolism, Herpesvirus 1, Human drug effects, Humans, Purine Nucleosides chemistry, Purine Nucleosides pharmacology, Stereoisomerism, Vero Cells, Adenosine Deaminase metabolism, Antiviral Agents metabolism, Benzoxazines chemistry, Purine Nucleosides biosynthesis
- Abstract
A series of ribo- and deoxyribonucleosides bearing 2-aminopurine as a nucleobase with 7,8-difluoro- 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (conjugated directly or through an aminohexanoyl spacer) was synthesized using an enzymatic transglycosylation reaction. Nucleosides 3-6 were resistant to deamination under action of adenosine deaminase (ADA) Escherichia coli and ADA from calf intestine. The antiviral activity of the modified nucleosides was evaluated against herpes simplex virus type 1 (HSV-1, strain L2). It has been shown that at sub-toxic concentrations, nucleoside (S)-4-[2-amino-9-(β-D-ribofuranosyl)-purin-6-yl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine exhibit significant antiviral activity (SI > 32) on the model of HSV-1 in vitro, including an acyclovir-resistant virus strain (HSV-1, strain L2/R)., (© 2018 John Wiley & Sons A/S.)
- Published
- 2019
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29. [AntiHIV/AIDS drug 6HP: antiviral activity, pre-clinical study. Efficiency in adult HIV-infected patients.]
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Galegov GA and Andronova VL
- Subjects
- Acquired Immunodeficiency Syndrome metabolism, Acquired Immunodeficiency Syndrome pathology, Adult, Animals, Anti-HIV Agents chemistry, Drug Evaluation, Preclinical, Humans, Thymidine chemistry, Acquired Immunodeficiency Syndrome drug therapy, Anti-HIV Agents therapeutic use, Thymidine analogs & derivatives, Thymidine therapeutic use
- Abstract
The new domestic antiretroviral drug 6HP, which is ammonium-3'-azido-3'-deoxythymidine-5'-carbomoylphosphonate, shows a high level of anti-HIV activity in cultures of lymphoblastoid cells. In a organism, the 6HP is converted to azidothymidine, and the its pharmacokinetic parameters indicate a prolonged nature of action of this compound in vivo. It is an important indicator that allows to formulate optimal therapeutic regimens during clinical application of 6HP. The complex of its antiviral properties and the results of its exhaustive preclinica study, as well as the results of studying its safety and tolerability in adult HIV-infected patients, including important first data of its use as a specific therapeutic antiHIV / AIDS drug, certainly indicate on its prospects and its usefulness in clinical use in patients with HIV infection, including as part of combination antiretroviral therapy., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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30. [The mechanism of stimforte action on herpesvirus infection.]
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Maldov DG, Andronova VL, Grigorian SS, Isaeva EI, Balakina AA, Terentyev AA, Ilyichev AV, and Galegov GA
- Subjects
- Animals, Brain drug effects, Brain metabolism, Brain virology, Gene Expression Regulation, Viral drug effects, Granzymes metabolism, Herpesviridae Infections blood, Herpesviridae Infections metabolism, Herpesviridae Infections virology, Herpesvirus 1, Human pathogenicity, Humans, Interferon-beta blood, Interferon-beta genetics, Interferon-beta metabolism, Interferon-gamma blood, Interferon-gamma genetics, Interferon-gamma metabolism, Killer Cells, Natural drug effects, Lung metabolism, Lung virology, Mice, Organic Chemicals therapeutic use, Virus Replication drug effects, Granzymes genetics, Herpesviridae Infections drug therapy, Herpesvirus 1, Human drug effects, Lung drug effects, Organic Chemicals pharmacology
- Abstract
Increased protease activity and a significant amount of granzyme B were observed in in organs of mice infected with acute herpes simplex virus HSV-1 with the introduction of Stimforte (100 or 250 µg/mouse). Thus, this drug activates killer cells, which play an extremely important role in the suppression of HSV-1 infection. Although the administration of Stimforte (100 μg/mouse) to intact mice results in the activation of IFN-β production and does not activate the production of IFN-λ, Stimforte administration to animals infected with HSV-1 reduces production of IFN-β in serum, brain and lungs, whereas the production of IFN-λ considerably increases as the result of administration of 100 μg/mouse of Stimforte., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
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31. Different effects of the immunostimulatory drug Stimforte on infections of hepatitis C virus and herpes simplex virus type 1.
- Author
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Maldov DG, Andronova VL, Grigorian SS, Isaeva EI, Deryabin PG, Mishin DV, Balakina AA, Ilyichev AV, Terentyev AA, and Galegov GA
- Subjects
- Animals, Antiviral Agents administration & dosage, Antiviral Agents therapeutic use, Chlorocebus aethiops, Hepacivirus drug effects, Hepacivirus physiology, Herpesvirus 1, Human drug effects, Herpesvirus 1, Human physiology, Immunologic Factors administration & dosage, Immunologic Factors therapeutic use, Interferons metabolism, Killer Cells, Natural drug effects, Male, Mice, Mice, Inbred BALB C, Vero Cells, Virus Replication drug effects, Antiviral Agents pharmacology, Hepatitis C drug therapy, Herpes Simplex drug therapy, Immunologic Factors pharmacology
- Abstract
Stimforte, an immune response-stimulating preparation, is active with respect to hepatitis C virus (HCV) and herpes simplex virus type I (HSV-1). The effects of Stimforte in animals infected with either HCV or HSV-1 are fundamentally different. In mice with acute herpes virus infection, Stimforte administration leads to a higher activity of natural killer cells and cytotoxic lymphocytes, and the amount of interferon (IFN) λ grows. In mice infected with HCV, Stimforte administration results in a significant increase in IFN-β but not IFN-λ in blood and affected organs. Stimforte has been found to affect directly HCV reproduction that causes the infected cell death, but it does not affect HSV-1 reproduction in the Vero cells (V).
- Published
- 2017
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32. INFLUENCE OF IMMUNOMODULATORY DRUG STIMFORTE ON THE EXPERIMENTAL HERPES VIRUS INFECTION IN COMBINATION WITH ACYCLOVIR AND ON HIV-INFECTION IN COMBINATION WITH RETROVIR.
- Author
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Maldov DG, Andronova VL, Kalnina LB, Ilyichev AV, Nosik DN, and Galegov GA
- Abstract
The combined action of the immunostimulatory drug Stimforte and the basic etiotropic drug acyclovir commonly used to treat herpes infections was studied using the model of lethal experimental infection of mice BALB/c with herpes simplex virus type 1. It was found that the interaction of these drugs is additive. In addition, Stimforte inhibits infection caused by a strain of virus, which is highly resistant to acyclovir. When administered 24 hours prior to HIV-1 infection of human lymphoblastoid cells MT-4, Stimforte exhibited reliable antiretroviral activity best expressed during the early period of infection (the 3rd day). On the 6th day of observation the effect was almost completely lost. Combined use of Stimforte at a dose of 50-100 µg/ml with a subthreshold dose of retrovir (0.03 µg/ml) had a synergistic antiviral effect. Thus, Stimforte, which exhibits, on the one hand, antiviral activity against viruses of different families and, on the other hand, the immunomodulatory properties, could be promising as an etiopathogenic tool in helping to normalize both nonspecific and specific immunity. It may be used simultaneously with etiotropic antiviral chemotherapy in treatment of generalized herpes infection in patients with immunodeficiency. Furthermore, Stimforte can be used in the case of development of drug resistance in HSV, in particular, in HIV-infected patients.
- Published
- 2017
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33. New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1.
- Author
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Kharitonova MI, Denisova AO, Andronova VL, Kayushin AL, Konstantinova ID, Kotovskaya SK, Galegov GA, Charushin VN, and Miroshnikov AI
- Subjects
- Acyclovir pharmacology, Antiviral Agents pharmacology, Cidofovir, Cytosine analogs & derivatives, Cytosine pharmacology, Drug Resistance, Viral drug effects, Foscarnet pharmacology, Herpesvirus 1, Human drug effects, Humans, Nucleosides pharmacology, Organophosphonates pharmacology, Antiviral Agents chemical synthesis, Benzimidazoles chemistry, Nucleosides chemistry
- Abstract
Using the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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34. Phosphazide (nikavir) is a highly effective drug for the treatment of HIV/AIDS infection.
- Author
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Galegov GA
- Subjects
- Anti-HIV Agents pharmacokinetics, Antiretroviral Therapy, Highly Active methods, Female, Fetus, HIV genetics, HIV metabolism, HIV Infections transmission, HIV Infections virology, Humans, Organophosphonates pharmacokinetics, Pregnancy, Pregnancy Complications, Infectious virology, Treatment Outcome, Zidovudine pharmacokinetics, Zidovudine therapeutic use, Anti-HIV Agents therapeutic use, HIV drug effects, HIV Infections drug therapy, Infectious Disease Transmission, Vertical prevention & control, Organophosphonates therapeutic use, Pregnancy Complications, Infectious drug therapy, Zidovudine analogs & derivatives
- Abstract
Federation Convincing evidence for high therapeutic activity and tolerability of Phosphazide in the treatment of HIV/AIDS-infection is given. Phosphazide is currently used in various regimens of highly active antiretroviral therapy, as well as in the HIV therapy in patients with simultaneously acquired chronic hepatitis C or tuberculosis. Therapeutic possibilities of Phosphazide were clearly manifested in the prevention of HIV transmission from mother to child. There is every reason to use Phosphazide in first-line antiretroviral therapy.
- Published
- 2017
35. Influence of the immunomodulatory drug stimforte on the humoral immune response in the experimental herpes virus infection.
- Author
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Maldov DG, Andronova VL, Balakina AA, Ilyichev AV, and Galegov GA
- Abstract
In the study of the immunostimulation preparation Stimforte activity using the model of the experimental herpes virus infection BALB/c, mice has shown that sera from mice treated with the drug on the 4th and 7th day after infection possessed a 3 times greater capability of specifically binding to the culture of HSV-1 (on cells Vero) according to dot blot analysis, as compared with intact infected mice sera obtained at the same time. It was also shown that these sera had a 5 times higher index of neutralization. On the basis of Western blots, it was detected that antibodies from sera of mice treated with Stimforte contacted the glycoproteins gB and gC of HSV-1 significantly better. Thus, Stimforte stimulates one of the strongest modulatory effects on the immune memory and is a promising drug for the treatment of chronic viral diseases.
- Published
- 2016
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36. [Interaction of Dystamycin Dimeric Analog with Poly(dA) x poly(dT), Poly[d(A-T)] x poly[d(A-T)] and Duplex O23 at Origin of Replication of the Herpes Simplex Virus].
- Author
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Surovaya AN, Bazhulina NP, Lepehina SY, Andronova VL, Galegov GA, Moiseeva ED, Grokhovsky SL, and Gursky GV
- Subjects
- Circular Dichroism, Nucleic Acid Conformation, Oligonucleotides chemistry, Poly A chemistry, Poly A genetics, Poly T chemistry, Poly T genetics, DNA Replication genetics, Replication Origin genetics, Simplexvirus chemistry
- Abstract
The binding of distamycin dimeric analog (Pt-bis-Dst) to poly[d(A-T)] x poly[d(A-T)1, poly(dA) x poly(dT) and duplex O23 with the sequence 5'-GCCAATATATATATATTATTAGG-3' which is present at the origin of replication of herpes simplex virus OriS is investigated with the use of UV and CD spectroscopy. The distinction of the synthetic polyamide from a natural antibiotic lies in the fact that in the synthetic polyamide there are two distamycin moieties bound via a glycine cis-diamino platinum group. It was shown that the binding of Pt-bis-Dst to poly[d(A-T)] x poly[d(A-T)] and poly(dA) x poly(dT) reaches saturation if one molecule of the ligand occurs at approximately every 8 bp. With further increase in the ratio of the added ligand to the base pairs in CD spectra of complexes with poly[d(A-T)] x poly[d(A-T)], we observed that the maximum wavelength band tend to be shifted towards longer wavelengths, while in the spectral region of 290-310 nm a "shoulder", that was absent in the spectra of the complexes obtained at low polymer coverages by the ligand, appeared. At high molar concentration ratios of ligand to oligonucleotide Pt-bis-Dst can bind to poly[d(A-T)] x poly[d(A-T)] in the form of hairpins or may form associates by the interaction between the distamycin moieties of neighboring molecules of Pt-bis-Dst. The structure of the complexes is stabilized by interactions between pirrolcarboxamide moieties of two molecules of Pt-bis-Dst adsorbed on adjacent overlapping binding sites. These interactions are probably also responsible for the concentration-dependent spectral changes observed during the formation of a complex between Pt-bis-Dst and poly[d(A-T)] x poly[d(A-T)]. Spectral changes are almost absent in binding of Pt-bis-Dst to poly(dA) x poly(dT). Binding of Pt-bis-Dst to duplex O23 reaches saturation if two ligand molecules occur in a duplex that contains a cluster of 18 AT pairs. With increasing the molar concentration ratio of the ligand to the duplex CD spectra undergo concentration-dependent changes similar to those observed during binding of Pt-bis-Dst to poly [d(A-T)] x poly[d(A-T)]. Testing for antiviral efficacy of Pt-bis-Dst showed that the concentration, at which the cytopathic effect produced by the herpes simplex virus in cell culture Vero E6 halved, is equal to 1.5 μg/ml and the selectivity index for evaluating antiviral activity is 65 at a relatively low cytotoxicity. The concentration of Pt-bis-Dst, at which approximately half the cells are killed, is equal to 100 μg/ml.
- Published
- 2016
37. Analysis of Antiviral Properties of Hexoral In Vitro against Some Viruses that Cause Acute Respiratory Infections and Herpes.
- Author
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Deryabin PG, Galegov GA, Andronova VA, and Botikov AG
- Subjects
- Animals, Cell Line, Chlorocebus aethiops, Dogs, Humans, Influenza A Virus, H5N1 Subtype drug effects, Influenza A Virus, H5N1 Subtype pathogenicity, Respiratory Tract Infections prevention & control, Vero Cells, Antiviral Agents pharmacology, Hexetidine pharmacology
- Abstract
Antiviral properties of Hexoral (0.1% solution and 0.2% aerosol for local application) and its constituent hexetidine against viruses causing human respiratory tract infections and herpes virus were studied in vitro. It was found that non-cytotoxic concentrations of hexetidine (alone and as a component of Hexoral) attenuated infectious properties of highly virulent influenza virus A/H5N1, pandemic influenza virus A/H1N1pdm, respiratory syncytial virus, and herpes simplex virus type 1 after a short-term exposure (30 sec) by 100 or more times. It was found that hexidine mostly contributes to the virucidal effect of Hexoral.
- Published
- 2016
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38. Study of Antiherpetic Efficiency of Phosphite of Acycloguanosine Ableto Over come the Barrier of Resistance to Acyclovir.
- Author
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Andronova VL, Jasko MV, Kukhanova MK, Galegov GA, Skoblov YS, and Kochetkov SN
- Abstract
As has been shown previously, phosphite of acycloguanosine (Hp-ACG) exhibits equal efficacy against ACV-sensitive and ACV-resistant HSV-1 strains in cell culture. Intraperitoneal administration of Hp-ACG to model mice with herpetic encephalitis caused by HSV-1 infection was shown to be effective in protecting against death. In the present work, we continue the study of the antiviral efficiency of Hp-ACG against HSV administered non-invasively; namely in vivo, orally and in the form of ointment formulations. It has been first shown that oral administration of Hp-ACG twice daily for five days prevents systemic infection in mice caused by HSV-1. Mortality in the control group of animals was 57%. Administration of Hp-ACG at doses of 600, 800 and 1,000 mg/kg per day significantly increased the survival and median day of death of the animals compared to the placebo-treated control group. A comparative evaluation of the therapeutic efficacy parameters of polyethylene glycol-based ACV ointment and Hp-ACG ointment was carried out after a 5-day course in the model of an experimental cutaneous infection of HSV-1 in guinea pigs. It was found that Hp-ACG has a significant therapeutic effect resulting in a statistically significant reduction in the lesion's surface area and the amount of vesicular structures. The exhibited therapeutic effect of 10% Hp-ACG in ointment form compares well with that of 5% ACG ointment.
- Published
- 2016
39. Effect of dimeric netropsin analogue 15Lys-bis-Nt and acyclovir on the reproduction of herpes simplex virus type 1. The search for variants of herpes virus with drug resistance to 15Lys-bis-Nt and acyclovir.
- Author
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Andronova VL, Grokhovsky SL, Surovaya AN, Gursky GV, and Galegov GA
- Subjects
- Amino Acid Sequence, Animals, Antiviral Agents chemistry, Chlorocebus aethiops, Dimerization, Dose-Response Relationship, Drug, Drug Interactions, Drug Resistance, Viral genetics, Herpesvirus 1, Human genetics, Herpesvirus 1, Human physiology, Molecular Sequence Data, Molecular Structure, Netropsin chemistry, Vero Cells, Acyclovir pharmacology, Antiviral Agents pharmacology, Herpesvirus 1, Human drug effects, Netropsin analogs & derivatives, Virus Replication drug effects
- Published
- 2015
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40. [The suppression of a herpes simplex virus reproduction with drug resistance by combination 15lys-bis-nt and phosphate of acycloguanosine with some antiherpetic drugs].
- Author
-
Andronova VL, Grokhovskiĭ SL, Deriabin PG, Gurskiĭ GV, Surovaia AN, Jas'ko MV, Kukhanova MK, Kochetkov SN, Skoblov IuS, and Galegov GA
- Subjects
- Acyclovir administration & dosage, Animals, Antiviral Agents administration & dosage, Chlorocebus aethiops, Drug Resistance, Viral drug effects, Drug Resistance, Viral genetics, Drug Synergism, Herpes Simplex genetics, Herpes Simplex virology, Simplexvirus growth & development, Vero Cells, Herpes Simplex drug therapy, Simplexvirus drug effects, Simplexvirus genetics, Virus Replication drug effects
- Abstract
Antiherpetic activity of the double and triple combinations, including original connections 15Lys-bis-Nt and phosphate of acycloguanosine (P-ACG), was studied in vitro. For the first time, it was demonstrated that in case of their combined use with known antiherpetic agents, whose activity does not depend on TK of HSV (PFA, AraA, CDV, Rib, GLN, αa-IFN), synergistic or additive effects of interaction was observed. The antiviral effect of the tested combinations was studied on the model of ACG-resistant viral strain. The tested combinations could be of interest for practical medicine.
- Published
- 2014
41. The combination of ribavirin and ozeltamivir effectively inhibits reproduction of influenza A virus resistant to rimantadine (amantadine) in vitro and in vivo.
- Author
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Deryabin PG, Galegov GA, Konstantinova ID, Muzyka IS, Miroshnikov AI, and L'vov DK
- Subjects
- Amantadine pharmacology, Animals, Antiviral Agents administration & dosage, Antiviral Agents therapeutic use, Dogs, Drug Combinations, Drug Resistance, Viral, Influenza A virus physiology, Madin Darby Canine Kidney Cells, Mice, Oseltamivir administration & dosage, Oseltamivir therapeutic use, Ribavirin administration & dosage, Ribavirin therapeutic use, Antiviral Agents pharmacology, Influenza A virus drug effects, Orthomyxoviridae Infections drug therapy, Oseltamivir pharmacology, Ribavirin pharmacology, Virus Replication drug effects
- Published
- 2014
- Full Text
- View/download PDF
42. [Research of suppression of the herpes simplex virus reproduction with drug resistance using a combination 15-Lys-bis-Nt with some antiherpetic drugs].
- Author
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Andronova VL, Grokhovskiĭ SL, Surovaia AN, Deriabin PG, Gurskiĭ GV, and Galegov GA
- Subjects
- Animals, Antiviral Agents chemistry, Chlorocebus aethiops, Dose-Response Relationship, Drug, Herpes Simplex metabolism, Humans, Vero Cells, Antiviral Agents pharmacology, Herpes Simplex drug therapy, Herpesvirus 1, Human physiology, Virus Replication drug effects
- Abstract
The antiviral effect of combinations of netropsin derivative 15-Lys-bis-Nt with the known antiherpetic compounds, whose activity does not depend on viral TK and which are able to inhibit replication of HSV in most cases, including strains resistant to acyclovir and pencyclovir, was studied. The combinations evoking additive, synergistic and significant synergistic effects of interaction of tested compounds were observed. The results obtained in this work indicated the possibility of significant reduction of concentrations of high toxic compounds in case of the combined use.
- Published
- 2014
43. [Stimforte action on the main inflammation characteristics in experimental animals contaminated by Herpes simplex-1].
- Author
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Mal'dov DG, Galegov GA, Andronova VL, Il'ichev AV, and Bel'kov AP
- Subjects
- Animals, Brain immunology, Brain virology, Herpes Simplex immunology, Herpes Simplex virology, Herpesvirus 1, Human growth & development, Immunomodulation, Inflammation drug therapy, Inflammation immunology, Inflammation virology, Lipid Peroxidation drug effects, Lung immunology, Lung virology, Male, Mice, Mice, Inbred BALB C, Oxidative Stress, Proteolysis, Thiobarbituric Acid Reactive Substances metabolism, Viral Load drug effects, Virus Replication drug effects, Brain drug effects, Herpes Simplex drug therapy, Herpesvirus 1, Human drug effects, Immunologic Factors pharmacology, Lung drug effects
- Abstract
In the brain and lungs of the experimental animals contaminated by Herpes simplex-1 there were detected much higher levels of the thiobarbituric acid-stained lipid oxidation products and proteolytic activity, evident of the inflammation process. Stimforte lowered the inflammation indices to the level, close to that in the brain of the noninfected animals. Yet the drug provided lower titers of the virus in the brain, lungs and serum in the contaminated animals and arrested the infection process by stimulation of the immune system. The mechanism of the inflammation suppression is discussed.
- Published
- 2014
44. [Substances from pyrolised tissues of reptile carcases differently modulate immunity of mammals of both sexes].
- Author
-
Mal'dov DG, Bel'kov AP, Il'ichev AV, Astashkin EI, Grigorian SS, Andronova VL, and Galegov GA
- Subjects
- Animals, Cardiovirus Infections drug therapy, Cardiovirus Infections virology, Complex Mixtures isolation & purification, Coronavirus Infections drug therapy, Coronavirus Infections virology, Encephalomyocarditis virus drug effects, Encephalomyocarditis virus physiology, Female, Hepatitis, Viral, Animal drug therapy, Hepatitis, Viral, Animal virology, Herpes Simplex drug therapy, Herpes Simplex virology, Herpesvirus 1, Human drug effects, Herpesvirus 1, Human physiology, Humans, Male, Mice, Murine hepatitis virus drug effects, Murine hepatitis virus physiology, NADPH Oxidases metabolism, Neutrophils cytology, Neutrophils immunology, Protein Kinase C metabolism, Reptiles metabolism, Sex Factors, Complex Mixtures pharmacology, Immunity, Innate drug effects, NADPH Oxidases antagonists & inhibitors, Neutrophils drug effects, Protein Kinase C antagonists & inhibitors, Viral Load drug effects
- Abstract
Substances with gender action on immunity were detected in water soluble hydrolised matter from reptile carcases. The gender action was shown on isolated blood neutrophils, whole blood and in vivo by the antiviral activity on experimental animals, contaminated with three types of viruses: Herpes simplex type 1, the virus of encephalomyocarditis and the virus of hepatitis of mice. The possible mechanism of the inhibitory action on the male immunity was associated with the protein kinase cascade, including protein kinase C, activated by phorbolmyristate in the cells of the immune system.
- Published
- 2014
45. [Research of suppression of the herpes simplex virus reproduction with drug resistance by combination phosphite of acycloguanosine with some antiherpetic drugs].
- Author
-
Andronova VL, Jasko MV, Kukhanova MK, Skoblov YS, Deryabin PG, and Galegov GA
- Subjects
- Animals, Chlorocebus aethiops, Cidofovir, Cytosine analogs & derivatives, Cytosine pharmacology, Drug Resistance, Viral physiology, Drug Synergism, Drug Therapy, Combination, Foscarnet pharmacology, Glycyrrhizic Acid pharmacology, Herpesvirus 1, Human physiology, Humans, Interferon-alpha pharmacology, Organophosphonates pharmacology, Phosphites, Ribavirin pharmacology, Vero Cells, Vidarabine pharmacology, Virus Replication drug effects, Acyclovir pharmacology, Antiviral Agents pharmacology, Herpesvirus 1, Human drug effects
- Abstract
The activity of the phosphite of acycloguanosine (P-ACG) and six antivirals was tested individually and in double and triple combinations on two strains of the herpes simplex virus (HSV) type 1 (sensitive to acyclovir and resistant to acyclovir) using the CPE inhibition method in the Vero E6 cell microcultures. These are: phosphite of acycloguanosine (P-ACG), Ara-A, cidofovir (CDV), ribavirin (Rib), phosphonoformate (PFA), glycyrrhizic acid (GLN) and alpha-interferon (alpha-IFN). All studied double combinations and triple combinations including P-ACV inhibited replication of both HSV strains more effectively than any drug alone. Various types of interactions depending on the virus type were observed in both viral models: synergistic (double combinations P-ACG with PFA, CDV, Rib, alpha-IFN and triple combinations P-ACG with alpha-IFN +PFA, alpha-IFN +AraA, alpha-IFN +CDV, PFA+CDV, PFA+Rib, CDV+AraA, CDV+Rib, CDV+GLN,PFA+AraA) and additive (P-ACG with AraA and PFA+GLN). Neither antagonism nor interference was noted for any combinations. Adduced results suggest that these combinations might be clinically useful for the treatment of certain herpes simplex virus type 1 infections.
- Published
- 2014
46. [The arsenolysis reaction in the biotechnological method of synthesis of the ribavirin. Inhibition of reproduction of influenza A virus with the combination of ribavirin and ozeltamivir in experiments in vitro and in vivo].
- Author
-
Konstantinova ID, Fateev IV, Galegov GA, Deriabin PG, Botikov AG, Muzyka IS, L'vov DK, and Miroshnikov AI
- Subjects
- Animals, Arsenates chemical synthesis, Arsenates chemistry, Dogs, Drug Combinations, Humans, Influenza, Human virology, Madin Darby Canine Kidney Cells, Mice, Oseltamivir administration & dosage, Ribavirin analogs & derivatives, Ribavirin chemical synthesis, Influenza A virus drug effects, Influenza, Human drug therapy, Ribavirin administration & dosage, Virus Replication drug effects
- Abstract
Improved biotechnological method of receiving the antiviral drug ribavirin by the reaction of transglycosilation by addition of catalytic amounts of sodium arsenate in the reaction mixture. Such approach allows to hydrolyze the amount of the excess natural nucleoside donor--ribose and, as a consequence, to simplify the composition of the reaction mixture and the process of separation of ribavirin. The effect of ribavirin and ozeltamivir carboxylate and their combination on the reproduction of the virus of the influenza A in cell culture and in experiments on laboratory animals (mouse Balb/C). The greatest anti-influenza effect is observed when using a combination of drugs, as compared to each of them taken separately.
- Published
- 2013
- Full Text
- View/download PDF
47. [Molecular-genetic analysis of DNA pol and TK of HSV-1 population using NGS technology].
- Author
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Gus'kova AA, Skoblov MIu, Lavrov AV, Zubtsov DA, Andronova VL, Gol'dshteĭn DV, Galegov GA, and Skoblov IuS
- Subjects
- Animals, Chlorocebus aethiops, Polymerase Chain Reaction, Sequence Analysis, DNA methods, Vero Cells virology, DNA-Directed DNA Polymerase genetics, Exodeoxyribonucleases genetics, Herpesvirus 1, Human genetics, Thymidine Kinase genetics, Viral Proteins genetics
- Abstract
It was determined the ratio of viral DNA and DNA from Vero cells using the polymerase chain reaction in real time in Vero cell lysate, infected with L2 strain of the herpes simplex virus type 1. Copy number of the virus reached a maximum after 24 hours of incubation of infection. Total DNA was isolated and sequenced using NGS technology by Ion Torrent device. Nucleotide sequences of the thymidine kinase gene (UL23) and DNA polymerase (UL30) were determined for a population of HSV-1 strain L2. Comparison of the primary structure of these genes with the corresponding nucleotide sequences of known strains of HSV-1 KOS and 17 was conducted. Differences in the structure of genes UL23 and UL30 between strain L2 and reference strains KOS and 17 are not important, because changes are found in non-conservative regions.
- Published
- 2013
- Full Text
- View/download PDF
48. [Estimation of activity of bis-netropsin derivatives based on a model of an experimental cutaneous herpes simplex virus disease of guinea pigs].
- Author
-
andronova VL, Grokhovskiĭ SL, Surovaia AN, Gurskiĭ GV, Deriabin PG, L'vov DK, and Galegov GA
- Subjects
- Acyclovir pharmacology, Administration, Topical, Animals, Disease Models, Animal, Guinea Pigs, Herpes Simplex pathology, Male, Ointments, Antiviral Agents pharmacology, Herpes Simplex drug therapy, Herpesvirus 1, Human, Netropsin analogs & derivatives, Netropsin pharmacology
- Abstract
Using the model of an experimental cutaneous infection of guinea pig males caused by herpes simple virus type 1, it is shown that application of dimerico derivatives of netropsin Lys-bis Nt and 15Lys-bis Nt in the form of polietilenglicol-based ointment suppresses viral infection more effectively than acyclovir.
- Published
- 2013
49. Phosphoramidate derivatives of acyclovir: synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro.
- Author
-
Zakirova NF, Shipitsyn AV, Jasko MV, Prokofjeva MM, Andronova VL, Galegov GA, Prassolov VS, and Kochetkov SN
- Subjects
- Acyclovir chemical synthesis, Animals, Antiviral Agents chemical synthesis, Chlorocebus aethiops, HEK293 Cells, HIV Infections drug therapy, Herpes Simplex drug therapy, Humans, Vero Cells, Virus Replication drug effects, Acyclovir analogs & derivatives, Acyclovir pharmacology, Antiviral Agents chemistry, Antiviral Agents pharmacology, HIV-1 drug effects, Herpesvirus 1, Human drug effects
- Abstract
The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
50. [Antiherpetic activity of netropsin derivatives as tested in experiments in laboratory animals].
- Author
-
Andronova VL, Grokhovskiĭ SL, Deriabin PG, Gurskiĭ GV, Galegov GA, and L'vov DK
- Subjects
- Animals, Brain drug effects, Chlorocebus aethiops, Herpes Simplex drug therapy, Herpes Simplex virology, Humans, Male, Mice, Mice, Inbred BALB C, Vero Cells, Antiviral Agents pharmacology, Brain virology, Herpesvirus 1, Human drug effects, Netropsin analogs & derivatives, Netropsin pharmacology
- Abstract
Two dimeric netropsin derivatives (Lys-bis-Nt 15Lys-bis-Nt) were comprehensively tested for antiviral and toxic activity in cell cultures and laboratory animals. The two compounds were found to provide effective and selective inhibition of reproduction of herpes simplex I both in cell culture Vero E6 and in brain of infected white mice, thereby increasing the survival rate and mean life expectation of treated animals as compared to control.
- Published
- 2012
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