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[Anti-influenza effect of bacterial RNAse and the pharmacokinetic basis of its administration in experimental studies]. / Protivogrippoznoe deistvie bakterial'noi RNKazy v éksperimente i farmakokineticheskoe obosnovanie sposoba vvedeniia ee v organizm.

Anti-influenzal action of bacterial and pancreatic RNAases was studied. It was shown in ovo that the RNAases had distinct virus inhibiting activity with respect to various strains of the grippe A virus and did not practically differ by their activity from remantadin but unlike it had inhibitory action on the grippe B virus. The anti-influenzal activity of bacterial RNAase in contrast to pancreatic one was detected not only in experiments with developing chick embryos but also in albino mice with lethal influenzal infection. The index of the animal protection by the preparation amounted to 54-90 per cent depending on the virus infecting dose and RNAase administration route, the lifespan of the animals being increased by 2.4 to 3.8 days. It was shown that the anti-influenzal effect of bacterial RNAase correlated with high levels of the exogenic enzyme in blood of the animals after the preparation intravenous administration. Elimination of RNAase was observed already within the first 4 hours after the experiment start. Intranasal administration allowed to increase the residence time of RNAase in blood up to 8 hours at the account of its gradual absorption from the administration site and the preparation availability increased more than 2-fold. The results provided the basis for recommending the intranasal route of bacterial RNAase administration for use in further investigation of RNAase antiviral activity.

[The effect of 3'-azido-2',3'-dideoxythymidine on experimental viral infections]. / Deistvie 3'-azido-2',3'-didezoksitimidina na éksperimental'nye virusnye infektsii.

3'-Azido-2',3'-dideoxythymidine (az-T) inhibited effectively the reproduction of some retroviruses; among these viruses were the four serological subgroups of sarcoma Raus virus in chicken embryo, avian myeloblastosis virus and erythroblastosis virus in chicken. This inhibition was specific towards retroviruses and practically was not observed in the case of infections DNA- and RNA-genome model viruses of vaccinia and influenza, at whose reproduction reverse transcriptase is not involved. Three other 3'-modified nucleosides did not block the above-listed retroviruses. For chickens, az-T showed low toxicity. The molecular mechanisms of the action of az-T are discussed.

[Molecular mechanisms of the antiviral activity of nucleoside analogs]. / Molekuliarnye mekhanizmy protivovirusnogo deistviia analogov nukleozidov.

The latest data are reviewed on the molecular biology mechanisms of antiviral effect exhibited by the analogues of nucleic acids components. Main effects of preparations used in medicine and virology are analyzed. The data are presented in proof of the existence of different as well as common pathways for virus inhibiting effects of different preparations. The pathways include the analogue interference with virus specific DNA-polymerases, affecting the posttranscriptional processes, etc.

[Inactivation characteristics of polyene macrolide antibiotics]. / Nekotorye osobennosti inaktivatsii polienovykh makrolidnykh antibiotikov.

Roseofungin, a pentaen was used as an example in investigation of certain characteristics of inactivation of polyenic antibiotics. An inactivation product of the antibiotic having no antiviral or antimycotic activity was isolated by TLC and column chromatography on Sefadex LH-20. UV, IR and EPR spectroscopy showed that this product was cys-tetraen without conjugation of the lactone carbonyl to the polyenic system.

Interfering activity of epidemic, attenuated and recombinant strains of influenza A virus.

Interfering activity (IA) of the epidemic and attenuated influenza virus strains of different ts-phenotype was studied. IA was assessed by inhibition of vaccinia virus cytopathic effect in chick embryo chorioallantoic membrane (CAM) cells. Direct relationship was established between the temperature sensitivity (ts) index and IA of these viruses. The relationship between IA and multiplicity of infection was strain-specific.

[Virus-inhibiting properties of the carbonyl-conjugated pentaene roseofungin]. / Virusingibiruiushchie svoistva karbonil-kon'iugirovannogo pentaena rozeofungina.

The antiinfluenza activity of roseofungin, a polyenic macrolide antibiotic was studied in vitro on surviving fragments of the chick embryo chorionallantoic membranes and in ovo on growing chick embryos. It was shown that the antibiotic activity against influenza A and B viruses was sufficiently high. The activity of roseofungin against influenza A virus did not differ from that of remantadin, the most active inhibitor of influenza virus reproduction. However, the activity of roseofungin against influenza B virus was an advantage of this antibiotic over remantadin, which had practically no effect on this virus type. A statistically significant protective effect of roseofungin (p less than 0.05) was shown on the animals with experimental influenza. The study on the antiviral activity of roseofungin against the DNA-containing variolovaccine virus revealed that it markedly inhibited the plague reduction. Roseofungin had a pronounced inhibitory effect on cell neoplastic transformation induced by the RNA-containing oncogenic virus of Rous sarcoma.

[Interaction of the polyene antibiotic nystatin with bivalent copper ions]. / Osobennosti vzaimodeistviia polienovogo antibiotika nistatina s ionami dvukhvalentnoi medi.

Characteristic features of interaction of nystatin with bivalent copper salts in water, methanol and dimethylsulfoxide were studied. It was shown that stable compounds of copper and nystatin at ratios of 1 : 2 and 1 : 4 formed in the above solvents. The antibiotic in these compounds was in an inert, native or activated state. Physicochemical and biological properties of the compounds were investigated.

[Antiviral action of carbonyl-conjugated pentaene macrolides]. / Protivovirusnoe deistvie karbonil-kon"iugirovannykh pentaenovykh makrolidov.

Clear antiviral activity of carbonyl-conjugated pentaene macrolides, such as flavofungin, mycothicin, brunefungin and flavopentin was shown on models with infectious and oncogenic viruses. The antibiotics were active against influenza A and B virus. The effect was most pronounced in the in vitro and in ovo systems. On a model of experimental influenza infection of mice with the lethal outcome, antiinfluenzal activity of flavofungin was comparable to that of remantadin. However, unlike the latter one flavofungin and brunefungin inhibited the growth of influenza B virus. The drugs had a pronounced inhibitory effect on variolavaccine virus and prevented formation of foci of cell neoplastic transformation infected with various strains of Rous sarcoma virus.

[Molecular mechanism of combined effect of amphotericin B and cyclophosphamide on a virus-induced neoplastic process]. / Molekuliarnyi mekhanizm sochetannogo deistviia amfoteritsina B i tsiklofosfana na virusindutsirovannyi neoplasticheskii protsess.

Study of an experimental neoplastic process induced by virus type strains of Rous's sarcoma has shown that amphotericin B potentiates antineoplastic action of cyclophosphamide. Administration of cytostatin does not affect the fractional composition of chromatin proteins. Administration of polyene changes this indicator, the changes being greater after combined use of both drugs. The character of a considerable part of the abnormalities in the fractional composition of chromatin proteins indicates that chromatin had been exposed to proteolytic enzymes.

Correlation between reproductive and interfering activities of epidemic and thermosensitive influenza virus strains.

Differences in interfering activities were demonstrated between low-passage epidemic and thermosensitive cold-adapted strains of influenza viruses A and B in experiments on chick embryos inoculated on the chorioallantoic membranes and on white mice. At a high multiplicity of infection the thermosensitive variants showed a higher interfering activity as compared with the original viruses which had undergone a limited number of chick embryo passages.

[Use of luminescent analysis for studying the characteristics of the virus-inhibiting action of polyene antibiotics]. / Ispol'zovanie liuminestsentnogo analiza dlia izucheniia osobennostei virusingibiruiushchego deistviia polienovykh antibiotikov.

The inhibitory effect of flavopentin was shown on the models of infectious and oncogenic viruses. Flavopentin is a polyenic antibiotic belonging to pentaenes. The characteristic features of the polyene interaction with the plasma membrane of the host cell were defined with the use of the luminescence analysis, when the antibiotic was applied with the therapeutic or prophylactic purposes in experimental influenzal infection.

[Changes in the state of plasma membrane proteins of tumor cells exposed to a polyene antibiotic and cyclophosphamide]. / Izmenenie sostoianiia belkov plazmaticheskikh membran opukholevykh kletok pod vozdeistviem polienovogo antibiotika i tsiklofosfana.

The fractional composition of the proteins of the plasmatic membranes of the Ehrlich's tumor cells treated with various drugs was studied with the use of electrophoresis in polyacrylamide gel. It was shown that the character of the changes in the fractional composition of the plasmatic membrane proteins under the effect of levorin and cyclophosphamide was different. When the drugs were used in combination, summation of the changes induced by every drug alone was observed. Possible causes of the changes in the fractional composition of the membrane proteins are discussed.

[Increase in the specific activity of killed influenza vaccines by using polyene antibiotics]. / Povyshenie spetsificheskoi aktivnosti ubitykh grippoznykh vaktsin s pomoshch'iu polienovykh antibiotikov.

It was shown experimentally that polyenic antibiotics, i. e. amphotericin B and sodium levorin markedly increased the specific immunogenic properties and interferonogenic activity of inactivated influenza virus vaccine prepared with various methods from highly reproductive recombinants. The rate of pneumonia and death from influenza among the vaccinated mice treated with inactivated influenza virus vaccine and one of the polyenic antibiotics was lower than that among the animals treated with the vaccine alone (P less than 0.05). Correlation between the increase in the immunological response, the decrease in the virus reproduction rate in the lungs and addition of the antibiotics into the vaccine was also observed. It is recommended that inactivated influenza virus vaccine be used in conjunction with polyenic antibiotics.

[Effect of polyene antibiotics on the increase in specific resistance due to inactivated antiviral vaccines]. / Vliianie polienovykh antibiotikov na povyshenie spetsificheskoi rezistentnosti, vyzvannoi inaktivirovannymi protivovirusnymi vaktsinami.

The capacity of polyenic antibiotics, such as water soluble forms of amphotericin B, mycoheptin, nystatin and levorin to stimulate immunogenicity and interferonogenic activity of inactivated antiviral vaccines was shown. The protective effect of the vaccine against rabies or forest-spring encephalitis in albino mice was more pronounced on its two-fold use in combination with the antibiotic than that on its use alone. The most significant results were obtained with highly diluted vaccines supplemented with amphotericin B. In this case the resistance index was 2 times higher than on vaccination without amphotericin B. In comparative assays of 4 various lots of vaccines against rabies the ED50 of every inactivated vaccine corresponded to thrice as low levels of the antirabies antigen than on vaccination without the polyen. The problems of the mode of action of the polyenic antibiotics and antiviral inactivated vaccines used in combination are discussed.