[New properties of trental as an inhibitor of viral activity with a wide range of activity]. / Novye svoistva trentala kak ingibitor virusnoi aktivnosti shirokogo spektra deistviia.

Experimental investigations on the spectrum and degree of the expression of trental antiviral activity were carried out. The investigations were done in cell cultures and laboratory animals using laboratory strains (including drug-resistant ones) of 13 viruses, causative agents of human and animal infections. The drug demonstrated its activity against 8 viruses of 7 families. It was highly active against 5 viruses: herpes simplex virus (including its acyclovir-resistant strain), vaccinia virus (including its methisazone-resistant strain), rotavirus and tick-borne encephalitis virus. As regards other viruses, its activity was less pronounced (hepatitis JA virus) or low (vesicular stomatitis virus, West Nile virus). It was concluded that, being a cardiovascular drug, trental was an effective broad spectrum virus inhibitor.

[Compounds, similar to acyclovir. VIII. Synthesis and antiviral activity of (R/S)-5-hydroxy-4-hydroxymethyl-3-oxapent-2-yl derivatives of nucleic bases]. / Soedineniia, podobnye atsikloviru. VIII. Sintez i protivovirusnaia aktivnost' (R/S)-5-gidroksi-4-gidroksimetil-3-oksapent-2-il'nykh proizvodnykh nucleinovykh osnovanii.

The (R/S)-5-hydroxy-4-hydroxymethyl-3-oxapent-2-yl derivatives of the uracil, thymidine, cytosine, adenine, guanine and 1,2,4-triazol-3-carboxamide were synthesized using 1,3-diacetoxy-2-(1-acetoxy)propane and 1,3-dichloro-2-(1-chlorethoxy)propane as alkylating agents. The guanine derivatives exhibited activity against HSV-1 (chemotherapeutic index 32).

[Antiviral properties of various pharmacologic groups of drugs]. / Antivirusnye svoistva razlichnykh farmakologicheskikh grupp preparatov.

Currently used cardiovascular drugs such as nicotinamide, strophanthin, corglycon, curantyl, cavinton, papaverin hydrochloride, nicotinic acid, xantinole nicotinate, isoptin, parmidin and halidor were studied by the program of antiviral drug screening. The majority of them (9 out of 11) were shown to have antiviral activity which was rather individual by its specificity and level. Laboratory strains of 9 viruses inducing the most common infections in man and animals, i.e. Herpes simplex, poxvaccine, influenza, vesicular stomatitis, respiratory syncytial infection, VEE, ECHO. Lassa fever and rotavirus infection were tested. The characteristic feature of the drugs was their high specific activity against the DNA-containing viruses and rotavirus. The three drugs papaverin hydrochloride, strophanthin and corglycon proved to be the most promising. Their antiviral activity was confirmed on a model of herpes infection in mice. The paper discusses whether the phenomenon discovered in the official drugs is important in the therapy of somatic patients.

[Lipid metabolism in experimental virus infections]. / Lipidnyi obmen pri virusnykh infektsiiakh v éksperimente.

The effect of herpes simplex virus (HSV) and influenza virus (IV) on lipid metabolism was studied. In conditions of acute herpetic infection of rabbits we detected typical dyslipidemia, characterized by increased contents of total cholesterol, beta-cholesterol and triglycerides in the absence of trustworthy differences in concentrations of alpha-cholesterol. The use of antiherpetic preparation furavir, on the background of infection, corrected lipid spectrum of the infected animals. Blood lipid disturbances in acute influenza virus infection of mice were not detected. HSV infection of cell culture of human aorta was accompanied by increased accumulation of free lipids in cells. IV infection, in the same conditions of experiment, did not change the contents of intracellular lipids. The obtained data deepen the existing notions of herpetic and influenza infections pathogenesis and may be useful in understanding etiopathogenesis of certain somatic metabolism diseases.

[The suppression of cellular Na+/H+ exchange leads to the inhibition of influenza virus activity]. / Podavlenie kletochnogo Na+/H+-obmena privodit k ingibirovaniiu aktivnoosti virusa grippa.

It was shown that amiloride, orthovanade and uabain induced almost a two-fold decrease in the rate of incubation medium oxidation by the chick embryo fibroblasts due to the Na+/H+ exchange and inhibited by more than 95 per cent the influenza virus activity. The following mechanism for inhibition of the influenza virus multiplication in the cells under the effect of the above mentioned substances was proposed: suppression of the cellular Na+/H+ exchange responsible for the decrease in pH value in the virus-carrying endosomes----prevention of the decrease in the intraendosomal pH value to the critical level----blocking of the acid dependent process of the virus uncoating----inhibition of the influenza infection as a whole.

[Compounds similar to acyclovir. VII. Attempts to construct an anti-herpetic agent (6-hydroxy-2-oxa-4-hexenyl derivatives of nucleic bases]. / Soedineniia, podobnye atsikloviru. VII. Popytka konstruirovaniia protivogerpeticheskogo preparata (6-gidroksi-2-oksa-4-geksenil'nye proizvodnye nukleinovykh osnovanii.

Based on the available data on the acyclovir's mechanism of action we attempted to predict the antiherpetic activity of 6-hydroxy-2-oxahexen-4-yl derivatives of nucleic bases. In terms of this model 9-(6-hydroxy-2-oxahexen-4-yl) guanine might be active. 6-Hydroxy-2-oxahexen-4-yl derivatives of adenine, guanine, cytosine, thymine, uracil, 1,2,4-triazole-3 and 1,2,4-triazole-5-carboxamide have been synthesized and their activity against herpes virus I investigated. The guanine derivative proved to possess rather high activity (chemotherapeutical index 8).

[Compounds, similar to acyclovir V. Synthesis and antiviral activity of carbethoxyalkoxymethyl derivatives of nucleic bases]. / Soedineniia, podobnye atsikloviru V. Sintez i protivovirusnaia aktivnost' karbétoksialkoksimetil'nykh proizvodnykh nukleinovykh osnovanii.

Ethyl esters and amides of carboxymethoxy-, alpha- and beta-carboxyethoxy- and gamma-carboxypropoxymethyl derivatives of adenine, guanine, cytosine, uracil, thymine, 1,2,4-triazole-3- and -5-carboxamide were synthesized and their antiviral activity was studied.

[Virus replication in a culture of smooth muscle cells from the human aorta]. / Replikatsiia virusov v kul'ture gladkomyshechnykh kletok aorty cheloveka.

A new modification of the method for cultivation of cells from blood vessel explants has been proposed, and on its basis several cell lines from different vessels of human embryo and adult subjects have been derived. The sensitivity of vessel cells to viruses was studied on a model of aorta cell culture using a wide spectrum of RNA and DNA viruses. All the strains under study with the exception of respiratory-syncytial virus (RSV) and encephalomyocarditis (EMC) virus induced a productive infection in the cells. The infection with RSV and EMC was abortive. The possibility of virus replication in vessel cells was confirmed by isolation of adenovirus from a human renal artery biopsy.

Isolation and basic properties of temperature--sensitive mutants of Venezuelan equine encephalomyelitis virus.

Fifteen temperature-sensitive (ts) mutants were isolated from 4 Venezuelan equine encephalomyelitis virus clones by nitrous acid treatment or by growing the virus in the presence of 5-fluoruracil. Three of them were classified as RNA- mutants by their inability to synthesize RNA at nonpermissive temperature (1.5-3.3% in respect to the wild type). The remaining 11 mutants showed a slight decrease of RNA synthesis at the nonpermissive temperature (32-73+) and were referred to the RNA+ phenotype. One mutant possessed RNA +/- phenotype (18%). Five complementation groups were determined by complementation analysis of the mutants.

[Preparation and characteristics of temperature-sensitive mutants of the Venezuelan equine encephalomyelitis virus]. / Poluchenie i kharakteristika temperaturochuvsvtitel'nykh mutantov virusa venesuél'skogo éntsefalomielita loshadei.

Fifteen ts mutants of Venezuelan equine encephalomyelitis (VEE) virus have been produced and studied. Two of them were isolated from a virus population grown in the presence of 5-fluorouracyl and 13 from a virus suspension treated with nitrous acid. The efficiency of plating 40 degrees/35 degrees of various mutants varied from 2 X 10(-2) to 6 X 10(-6). Three ts mutants had RNA- phenotype (RNA synthesis at a nonpermissive temperature was 1.5-3.3% of that of the wild type), 11 ts mutants had RNA+ phenotype (RNA synthesis decreased insignificantly, 32-75%), and one ts mutant was intermediate (18%).