[Synthesis and antiherpes activity of acyclovir phosphoesters]. / Sintez i antigerpeticheskaia aktivnost' fosfornykh éfirov atsiklovira.

9-(Hydroxyethyloxymethyl)guanine (acyclovir) phosphite and fluorophosphate were synthesized by the reactions of acyclovir with phosphorus trichloride in triethyl phosphate and with fluorophosphoric acid in the presence of 2,4,6-triisopropylbenzenesulfonyl chloride, respectively, and characterized by the data of 1H and 31P NMR and mass spectra. These products selectively inhibit reproduction of the herpes simplex virus type 1 in the Vero cell culture, the phosphite being also substantially active against a herpes virus strain resistant to acyclovir.

[Biotechnological synthesis of ribavirin. Effect of ribavirin and its various combinations on the reproduction of Vaccinia virus]. / Biotekhnologicheskii sposob polucheniia ribavirina. Deistvie ribavirina i nekotorykh ego kombinatsii na reproduktsiiu virusa ospovaktsiny (Vaccinia virus).

The biotechnological method of synthesis of ribavirin, vidarabin, and 6-azauridine by the use of immobilized recombinant enzymatic preparations of nucleoside phosphorylase was improved. The effect of ribavirin and its combinations with the other synthesized nucleosides on the reproduction of Vaccinia virus was studied using cultures of Vero cells. The combination of ribavirin and vidarabin was shown to provide an antiviral effect at lesser concentrations than when these compounds were taken separately. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 6; see also http://www.maik.ru.

[Effect of remantadine on the morphogenesis of the Venezuelan equine encephalomyelitis virus in a Vero cell culture]. / Vliianie remantadina na morfogenez virusa venesuél'skogo éntsefalomielita loshadei v kul'ture kletok Vero.

Morphogenesis of Venezuelan equine encephalomyelitis (VEE) virus was studied in Vero cell cultures with or without remantadine treatment. Remantadine was found to inhibit late stages of VEE virus morphogenesis, especially formation of virus cores in the cytoplasm of the infected cells.

[Combined effect of remantadine (alpha-methyl-1-adamantane methylamine) and ribovirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) on the reproduction of Sindbis virus in cell culture]. / Issledovanie kombinirovannogo deistviia remantadina (al'fa-metil-adamantanmetilamina) i ribovirina (1-beta-D-ribofuranozil-1,2,4-triazol-3-karboksamida) na reproduktsiiu virusa Sindbis v kul'ture kletok.

The influence of remantadine, ribovirine, and combination thereof on Sindbis virus reproduction in cell cultures was studied. Comparison of remantadine and ribovirine showed the former to be a stronger inhibitor of Sindbis virus reproduction. The results of the combined effect of both drugs in chick embryo fibroblast cultures showed undoubtful advantages of this treatment over the use of each of the drugs alone. In studies of the effect of ribovirine on synthesis of virus-specific proteins and RNA no inhibition of formation of virus-specific macromolecules was observed.

[Isolation of acyclovir-resistant strains of herpes simplex virus from clinical material]. / Izoliatsiia iz klinicheskogo materiala shtammov virusa gerpesa prostogo, obladaiushchikh rezistentnost'iu k antsikloviru.

A total of 115 strains of herpes simplex virus were isolated from clinical material collected in patients with genital herpes. The majority (93%) of isolated strains were sensitive to acyclovir: ID50 varied from 0.15 to 0.80 microgram/ml acyclovir. Eleven (7%) strains from 4 patients were resistant to acyclovir: ID50 was 30-125 times higher in comparison with the reference HSV-1 strain L2.

[Etiotropic medicinal therapy of viral infections]. / Etiotropnaia lekarstvennaia terapiia virusnykh infektsii.

The paper contains a description of modern data on etiotropic therapy (chemotherapy) for widespread and socially-significant viral infections, like influenza, acute respiratory lesions, herpes-virus infections, hepatitis, AIDS and other extra dangerous viral infections. The survey focuses on the contribution of Russian researchers to creating antiviral chemopreparations.

[High performance rapid method for estimating the sensitivity of viruses to synthetic compounds]. / Vysokoproizvoditel'nyi ékspress-metod dlia opredeleniia chuvstvitel'nosti virusov k sinteticheskim soedineniiam.

A high performance semiautomatic microprocedure was used. It provided reliable quantitative estimation of antiviral and toxic properties of synthetic compounds. The procedure is rapid, technologically simple and cost-effective.

[Effect of various adamantane compounds on the reproduction of Sindbis virus. Isolation and properties of a resistant strain]. / Izuchenie deistviia nekotorykh soedinenii adamantana na reproduktsiiu virusa sindbis. Poluchenie i svoistva rezistnogo shtamma.

Rimantadine and its structural analogs, i. e. amide of 1-adamantane carboxylic acid (AACA) and 1-adamantane acetic acid amide, were shown to be able to inhibit reproduction of Sindbis virus in culture Vero cells. AACA had the maximum antiviral activity. Subcultures of the initial sensitive population of Sindbis virus in the presence of AACA led to formation of mutants resistant to AACA as well as to rimantadine, adamantane acetic acid amide and ammonium chloride. The Sindbis virus population was heterogenous in sensitivity to AACA, which was evident from isolation of separate clones with various levels of sensitivity to the above mentioned compounds from the population. It was found that reproduction of the AACA sensitive and resistant strains of Sindbis virus differed: the latent period of the resistant strain was 2 hours longer than that of the sensitive strain. The same effect was observed in the comparative study on synthesis of the virus-specific RNA.

[Action of remantadine on virus-specific polypeptide synthesis in a Sindbis virus-infected cell culture]. / Deistvie remantadina na sintez virusspetsificheskikh polipeptidov v kul'ture kletok, infitsirovannykh virusom Sindbis.

Effect of remantadine (alpha-methyl-I-adamantane methylamine) on reproduction and synthesis of the virus-specific polypeptides was studied in culture of chicken embryo fibroblasts, infected with virus Syndbis. The preparation inhibited the virus reproduction as well as the formation of virus-specific proteins after addition into the cultural medium together with virus, immediately after absorption and within 1 and 2 hrs after absorption. The data obtained suggest a possibility of an immediate effect of remantadine on the synthesis of virus-specific macromolecules.

[Action of para-aminobenzoic acid and its combination with acyclovir in herpetic infection]. / Deistvie para-aminobenzoinoi kisloty i ee kombinatsii s atsiklovirom na gerpeticheskuiu infektsiiu.

The effect of para-amino benzoic acid (PABA) on the virus of Herpes simplex (VHS-1, strain L2) was studied and it was shown to be active in vitro and in vivo. The action of PABA was virucidal in the culture of the cell-free virus-containing material. It lowered the death rate of the laboratory mice with experimental herpetic encephalitis (intraperitoneal contamination) at the average by 40 per cent and increased the mean life-span of the animals significantly decreasing the virus titre in the mouse brain. PABA was not toxic with respect to the Vero cells thus not preventing the virus-induced cytopathic effect in the cultures. However, PABA showed high ability to potentiate the antiherpetic action of acyclovir (Zovirax, acycloguanosine) in the infected cultures when acyclovir was used in inactive concentrations.

[Mechanism of action of remantadine hydrochloride on Sindbis virus reproduction: inhibition of virus penetration into the cell]. / O mekhanizme deistviia solianokislogo remantadina na reproduktsiiu virusa Sindbis: ingibirovanie protsessa penetratsii virusa v kletku.

The effect of rimantadine and ammonium chloride on the RNA synthesis of Sindbis virus, added in different times of infection cycle, was studied. When compounds were presented in period of adsorption and first hour post-infection, the maximal inhibitory effect was found. The step blocked by rimantadine was identified as uncoating process (deprotainization). This connection was confirmed by the finding that rimantadine markedly reduced the change of the virus RNA into the nuclease-sensitive form.

[Effect of rimantadine on the synthesis of virus-specific RNA in the culture of cells infected with Sindbis virus]. / Vliianie rimantadina na sintez virusspetsificheskikh RNK v kul'ture kletok, infitsirovannykh virusom Sindbis

Effect of rimanthadine (alpha-methyl-I-adamantane methylamine) on the synthesis of virus specific RNA was studied in culture of cells, infected with Syndbis virus. Rimanthadine inhibits the synthesis of virus specific RNA beginning from the 3-rd hr of infection. A magnitude of inhibition from the 3-rd to the 7-th hrs of infection was practically the same and exceeded 50%. In the presence of rimanthadine "early" RNA was formed (with sedimentation constant of 20-14 S), where radioactivity was lowered as compared with control; formation of more "late" RNA peaks (43 S, 34 S and 26 S) was completely prevented within these periods of infection.

[Para-aminobenzoic acid--an interferon inducer]. / Paraaminobenzoinaia kislota--induktor interferona.

Para-aminobenzoic acid (PABA) was shown to be an early type interferon inductor. PABA (10 micrograms/ml) induced interferon production in vitro in the cells of human peripheral blood and in vivo in albino mice (10 mg/kg). The results of the study suggested that PABA was able to induce production of interferon-alpha/beta in various immunocyte populations. By its interferonogenic activity PABA was comparable with the known interferon inductors. One of the mechanisms of the previously described in vivo antiherpes action of PABA can be attributed to its interferon inducing activity.

[Para-aminobenzoic acid in therapy of experimental keratitis caused by herpes simplex virus in rabbits: the therapeutic effect and decrease of infectious titer]. / Para-aminobenzoinaia kislota v lechenii eksperimental'nogo keratita, vyzvannogo virusom prostogo gerpesa u krolikov: terapevticheskii effekt i snizhenie infektsionnogo titra.

Para-aminobenzoic acid (PABA) in low concentrations exerted an antiherpetic effect with a good therapeutic result in rabbits with experimental keratoconjunctivitis caused by herpes simplex virus (HSV) (experimental group). In group 2 (control) 0.9% NaCl solution was used as placebo. The animals were infected by instillation of HSV-1 on the cornea predissected with a bifurcation needle. The severity of keratitis was assessed in scores after A. A. Kasparov et al. PABA and placebo were administered starting from day 3 postinfection as subconjunctival injections and then instillations. In experimental group (5 rabbits, 10 eyes) the degree of keratitis reduced from 3.0 +/- 0.2 to 1.7 +/- 0.1 points within the first 4 days. Complete epithelialization was over by day 4.4 +/- 0.4, clinical cure was attained by days 12-13. In control group (6 rabbits, 12 eyes) erosion of the cornea and severity of keratitis increased from 2.9 +/- 0.07 to 3.8 +/- 0.2 points by day 4 postinoculation after placebo was started, after which it reduced; epithelialization was over by day 8.2 +/- 0.3, clinical cure by days 13-14. Infective titer in the cornea was determined in VERO cell culture from the degree of virus-induced cytopathogenic effect and expressed in lgTCE50. On day 13 this parameter was reliably higher in the control group in comparison with the experimental (3.2 vs. 1.8), this confirming the virucidal effect of PABA.

[Study of interferon-inducing activity of para-aminobenzoic acid injected subconjunctivally in rabbits]. / Izuchenie interferonindutsiruiushchei aktivnosti paraaminobenzoinoi kisloty v glazakh krolikov pri subkon''iunktival'nom vvedenii.

Para-aminobenzoic acid (PABA) is an early interferon inductor. The present study assesses the interferon-inducing activity of PABA (0.007 and 0.06% solutions) and poludan (Poly A:U) injected subconjunctivally to rabbits. Interferon (If) titer in the conjunctival washings and anterior chamber humor was assessed 4-48 h after injection of If inductors. After the first injection of 0.007% PABA, If titer in the conjunctival washings was constantly increasing and reached the maximum after 48 h (64-128 U/ml). Repeated injection of PABA after 5 days still more stimulated the production of If, with the peak after 24 h (128 U/ml); after 48 h the titer of If was still high. If titers induced by 0.007% PABA and poludan were compatible after both injections in the conjunctiva but not in the anterior chamber humor. With poludan, the maximum If titer (16 U/ml) was observed 6 h postinjection, after which it was no longer detected, while after PABA the maximum If titer (64 U/ml) was observed during the 4th and 12th hours postinjection and then decreased, remaining rather high after 24 h. After 0.06% PABA, If titers were 2-4 times lower in all experiments than after 0.007% PABA. The detected interferon-inducing activity of PABA suggests its therapeutic efficacy in ocular diseases involving disorders in If production.