[Inhibitory effect of various 3'-amino- and 3'-azido-3'-deoxyribonucleotide-5'-triphosphates on RNA synthesis, catalyzed by RNA polymerase of influenza type A virus and cellular RNA-polymerase]. / Ingibiruiushchee deistvie nekotorykh 3'-amino- i 3'-azido-3'-dezoksiribinukleozid-5'-trifosfatov na sintez RNK, kataliziruemyi RNK-polimeraznoi virusa grippa A i kletochnoi RNK-polimerazoi.

Some new analogues of ribonucleoside-5'-triphosphates modified in 3'-ribose position and base [CTP (3'NH2), CTP (3'NH2) (5Me), CTP (3'N3) (5 Me), RvTP (3'N3)] have been synthesized. The inhibitions of RNA-synthesis catalyzed by the influenza A viral RNA-polymerase in cell free system and by the RNA-polymerase II from mice liver in the system of cellular nuclei by these reagents have been compared. All the studied preparations efficiently inhibited the RNA-synthesis in both cases. The inhibitors modified only in 3'-ribose position did not express specificity to any of RNA-polymerases tested, while some analogues having two modification in the molecule demonstrated the selective inhibition of RNA-synthesis directed by the influenza A viral RNA-polymerase [ara GTP (3'NH2), RvTP (3'N3')].

[Inhibitory effect of 3'-azido-3'-azido-3'-deoxy- ribavirin-5'-triphosphate on RNA synthesis catalyzed by RNA polymerase from influenza A virus and by cellular DNA-dependent RNA polymerase II]. / Ingibiruiushchee deistvie 3'-azido-3'-dezoksiribavirin-5'- trifosfata na sintez RNK, kataliziruemyi RNK-polimerazoi virusa grippa A i kletochnoi DNK-zavisimoi RNK-polimerazoi II.

Inhibitory effect of 3'-azide-3'deoxy-ribavirin-5'-triphosphate on activity of RNA-dependent RNA polymerase from influenza A virus as well as on DNA-dependent RNA polymerase II from mice liver nuclei was studied. The drug inhibited effectively RNA synthesis catalyzed by these enzymes, whereas its most selective inhibitory action was found in reaction with RNA polymerase from influenza A virus.

[Comparative study of the RNA-polymerase activity of non-pathogenic and pathogenic influenza viruses A and B]. / Sravnitel'noe issledovanie aktivnosti RNK-polimerazy u nepatogennykh i patogennykh virusov grippa A i B.

Activity of RNA polymerase was studied in original non-pathogenic for mice viruses of influenza A and B (A/seal/Massachusetts 1/80, A/USSR 05/81, A/Philippines 2/82 and B/Singapore 227/79) and of their pathogenic derivatives. All the non-pathogenic viruses studied exhibited the low rate of transcriptase activity. Pathogenic derivatives of these strains exhibited higher activity of RNA polymerase, which was 1.5-3-fold higher as compared with the original strain. During passage of influenza viruses A and B in mice organism selection of the population appears to occur, which had the highest transcriptase activity.

[Inhibition of influenza virus A RNA-polymerase activity by various 3'-amino-3'-deoxy- and 3'-azido-3'-deoxyribonucleoside-5'-triphosphates]. / Ingibirovanie aktivnosti RNK-polimerazy virusa grippa A nekotorymi 3'-amino-3'-dezoksi- i 3'-azido-3'-dezoksiribonukleozid-5'-tri- fosfatami.

The effects of 3'-amino-3'-deoxy- and 3'-azido-3'-deoxyribonucleoside-5'-triphosphates on the RNA synthesis catalyzed by influenza virus A RNA polymerase were studied. All nucleotide analogues tested decreased the RNA synthesis twofold at the inhibitor: substrate ratio about 1:5 (in moles). The hypothetic mechanism of inhibitors action based on the incorporation of inhibitors into the 3'-termini of the RNA chains and subsequent blocking of the RNA chains elongation is proposed. The nucleotide analogues under investigation were several times more effective as compared with the ribavirine 5'-triphosphate, a well-known inhibitor of influenza A virus reproduction.

[Activity of virion RNA-polymerase in influenza A and B virus variants with different pathogenicities for mice]. / Aktivnost' virionnoi RNK-polimerazy u variantov virusa grippa A i B, razlichaiushchikhsia po priznaku patogennosti dlia myshei.

RNA polymerase activities in parental strains of influenza A and B viruses nonpathogenic for mice and their pathogenic variants have been studied. The parental strains are A/seal/Massachusetts 1/80, A/USSR 05/81, A/Philippines 2/82, B/Singapore 222/79. The RNA polymerase activity has been also studied in recombinant strains obtained by crossing various parental strains, one of which is pathogenic for mice (AR/PR 8/34), and having different degrees of pathogenicity. The nonpathogenic viruses had low transcriptase activity. RNA polymerase activity in pathogenic variants is shown to be 1.5-3 times higher than that in the parental strains. All the recombinants, whatever their pathogenicity, had approximately the same transcriptase activities which were 1.5-2 times higher than those registered in parental nonpathogenic strains.

[Inhibitory effect of deoxyadenylyl-(3'-5')-deoxyguanosine on the RNA-polymerase activity of influenza virus A]. / Ingibiruiushchee deistvie dezoksiadenilil-(3'-5')-dezoksiguanozina na aktivnost' RNK-polimerazy virusa grippa A.

Deoxyadenylylguanosine (dAdG, 0.2-0.4 mM), affecting the RNA polymerase activity, caused inhibition of transcription of the influenza A virus in presence of precursor AdG by 50-60% and a 80-85% inhibition in absence of the precursor. The inhibitor exhibited its effect independently on the time of addition into an incubation mixture. Addition of 0.5 mM inhibitor into a cultural medium inhibited reproduction of the influenza A virus in a culture of chicken embryonal fibroblasts.

[Kinetics of 3H-remantadine accumulation and excretion in the tissues of pregnant mice and their fetuses]. / Kinetika nakopleniia i vyvedeniia 3H-remantadina v tkaniakh beremennykh myshei i plodakh.

The authors studied the pharmacodynamics of remantadin in fetuses, liver, kidneys and spleen of pregnant mice after a single oral administration of 3H-remantadin in a dose of 2.8 mg/kg. Thirty to 60 min after the drug administration the fetuses and tissues showed the maximal amount of the drug penetrating an organ. The greatest amount of remantadin was detected in the liver, the least amount in the kidneys and fetuses. The drug half-life in organs and fetuses did not exceed 2 hours. Twelve hours after the drug administration the kidneys and spleen demonstrated remantadin traces (less than 0.1%), the fetuses showed 0.2% and the liver about 0.7% of the drug. It is concluded that remantadin is marked by good placenta permeability and that it is completely eliminated from the fetus.

[RNA-polymerase activity of pathogenic and nonpathogenic influenza A virus variants]. / Aktivnost' RNK-polimerazy patogennykh i nepatogennykh variantov virusov grippa A.

The transcriptase activity of original mouse-apathogenic strains of human (A/USSR/05/81) and animal (A/walrus/Massachusetts/1/80) influenza viruses and their pathogenic variants was studied. Also RNA-polymerase was studied in two types of antigenic recombinants produced by hybridization of the parental strains one of which (A/PR8/34) was pathogenic for mice. The nonpathogenic viruses under study were shown to have a low transcriptase activity, while pathogenic variants of these strains had a higher RNA-polymerase activity (1 1/2-3 times higher than in the original virus). All the recombinants tested, irrespective of their pathogenicity, had approximately similar transcriptase activity, 1 1/2-2 times higher than the enzymatic activity of the parental nonpathogenic virus.

[Dynamics of 3H-remantadine accumulation of elimination in mouse tissues]. / Dinamika nakopleniia i éliminatsii 3H-remantadina v tkaniakh myshei.

The dynamics of remantadine accumulation in and elimination from mouse tissues were studied by a radioactive method after a single oral administration of the drug to mice. The maximum accumulation of remantadine in their organs was observed 30 min after administration, the half-elimination period did not exceed 2 hours.

[Radioactive labeling by means of tritium atomic beam of some antivirus preparations]. / Vvedenie radioaktivnoi metki s pomoshch'iu atomarnogo puckha tritiia v nekotorye protivovirusyne preparaty.

Results are presented of 3H-labelling of antivirus preparations amantadine and rimantadine. They show possible application of 3H-amantadine and 3H-rimantadine obtained in virological investigations.

[Properties of DNA-dependent RNA-polymerase from spleens of mice infected with Rauscher leukemic virus]. / Svoistva DNK-zavisimykh RNK-polimeraz selezenki mushei, zarazhennykh virusom leikoza raushera.

The properties of RNA polymerases A, B and C isolated from the spleens of mice infected with Rauscher leukemic virus were studied. The solubilized RNA-polymerases A and B were purified 150--300-fold. The dynamic changes in the activities of all forms of RNA-polymerases at different stages of leukosis were studied. At the earliest steps of leukosis a 2-fold increase in the RNA-polymerase B activity followed by a 5-fold increase in the RNA-polymerase A activity was observed. At late stages of leukosis the activity of RNA-polymerase C also showed an increase. The properties of RNA-polymerases A and B from the spleens of virus-infected mice were compared to those of the controls. In leukemic tissues the specific activities of RNA-polymerases A and B were higher as compared to those of the enzymes isolated from the spleens of non-infected mice. However, no significant differences in the enzyme properties in normal and virus-infected animals were revealed. Dihydrorifampicine (200 mkg/ml) caused a 50% inhibition of RNA polymerase A in vitro but had no effect on the activities of RNA-polymerases B and C.

[Effect of methotrexate on the activity of DNA-dependent RNA polymerases (A and B) in the spleen of mice infected with Rauscher leukemia virus and on the development of virus-induced leukemia]. / Vliianie metotreksata na aktivnost' DNK-zavisimykh RNK-polimeraz (A i B) v selezenkakh myshei, zarazhennykh virusom leikoza Raushera, i na razvitie virusindutsirovannogo leikoza.

Methotrexate was shown to inhibit development of Rausher's leukosis and growth of spleen. Activity of DNA-dependent RNA polymerases A and B was distinctly altered. The activity of RNA polymerase B was increased two-fold within the first days of the leukosis development; RNA polymerase A was activated five-fold in the course of subsequent progression of the impairment. Methotrexate inhibited the RNA polymerase activity in leukemic spleens. As suggested by correlation between weight of the spleen and the activity of RNA polymerases A and B, the enzymatic activity may be considered as a marker of the leukosis development.

[Activity of DNA-dependent RNA polymerases A and B in spleen nuclei of mice infected with Rauscher leukemia virus]. / Aktivnost' DNK-zavisimoi RNK-polimerazy A i B v iadrakh selezenok myshei, zarazhennykh virusom leikoza Raushera

The activity of DNA-dependent RNA polymerase A and B in isolated nuclei of spleens of mice infected with Rauscher leukemia virus was studied. A 3-fold increase in the activity of both RNA-polymerases in leukemic spleens was established. Study of the properties of RNA-polymerase B from nuclei of spleens of mice infected with Rauscher virus in comparison with the enzyme from normal tissue revealed the existence of some specific features in the enzyme from leukemic cells. The nature of the increased activity of RNA-polymerase B in leukemic cells is discussed.