[Effect of ribamidil on the reproduction of the herpes simplex virus in a CV1 cell culture]. / Vliianie ribamidila na reproduktsiiu virusa prostogo gerpesa v kul'ture kletok CV1.

Cytotoxic properties and antiviral activity of abnormal nucleoside ribamidile were studied on the model of herpes simplex virus type 1 in CV1, continuous cell culture. The drug produced no cytotoxic effect even in concentrations of 500 and 250 micrograms/ml but had a marked capacity to inhibit herpes simplex virus reproduction in this system in concentrations of 125 and 62.5 micrograms/ml. Antiviral effect of ribamidile was enhanced by its combined use with 5'-deoxy-5'-fluorothymidine.

[Inhibiting action of adamantane derivatives on chronic influenzal infection in a tissue culture]. / Ingibiriruiushchee deistvie proizvodnykh adamantana na khronicheskuiu grippoznuiu infektsiiu v kul'ture tkanei.

Chronic influenza infection was produced by inoculation with influenza A virus, Waybridge strain (Hav1N1), of continuous murine leukemia Rauscher cells transformed by 20-methylcholantrene. The complete duration of the proliferative-destructive cycle of Rauscher/MX culture infected with fowl plague virus was 24 days on the average. The virus was found in the culture fluid virtually in all stages of the cycle, its titre reaching 10(7) EID50/ml at the peak of the destructive stage. By 14-15 days of the cycle in the chronically infected cells active synthesis of all virus-specific polypeptides (P1, P2, P3, HA, NP, M. NS) was observed, their electrophoretic mobility corresponding completely to that of proteins of the original influenza A virus strain. Simultaneously, almost complete inhibition of synthesis of cellular proteins is observed. Treatment of cultures with amantadine (12.5 micrograms/ml for 4 days) and remantadine (6.25 micrograms/ml for 7 days) interrupted the development of the infectious cycle for 2 1/2-3 1/2 months; during this time cellular protein synthesis recovered and no virus-specific polypeptides were formed. Then, the proliferative-destructive cycle reestablished in the infected cultures.

[Rapid method of producing influenza A virus variants resistant to amantadine and remantadine and their primary characteristics]. / Uskorennyi metod polucheniia variantov virusa grippa A, rezistentnykh k amantadinu i remantadinu, i ikh pervichnaia kharakteristika.

A rapid method for production of influenza A virus variants resistant to the adamantane series derivatives, amantadine and remantadine, has been developed. The method consisted of two stages. In the first, the virus was subjected to one passage in the presence of the preparations under a liquid overlayer in a one-cycle experiment. In the second stage, the resulting virus was titrated by the plaque method, the agar overlay containing the preparations in a concentration which was not toxic for the cells. Production of large and small plaques in the presence of the preparations in agar was an indication for selection of resistant virus variants and their further study. Cross-resistance of amantadine- and remantadine-resistant variants to remantadine and amantadine, respectively, was studied. No complete cross-resistance in these viruses could be demonstrated. The amantadine-resistant virus was not inhibited by remantadine, whereas the remantadine-resistant virus was significantly inhibited by amantadine as was demonstrated by both virological methods and by induction of RNA-dependent RNA polymerase and synthesis of viral proteins. The experimental results suggest that the mechanisms of formation of influenza A virus resistance to amantadine and remantadine are not absolutely identical.

[Effect of amantadine (1-aminoadamantane) and remantadine (alpha-methyl-1-adamantane methyl amine) hydrochlorides on formation of influenza A viral proteins]. / Sravnitel'noe izuchenie deistviia solianokislykh amantadina (1-aminoadamantana) i remantadina (al'fa-metil-1-adamantanmetilamina) na obrazovanie belkov virusa grippa A.

Inhibitory effect of amantadine (I-amino adamantane) and remantadine (alpha-methyl-1-adamantane methylamine) hydrochlorides on reproduction of influenza A virus as well as, in particular, on formation of virus specific proteins was studied in cell culture. These drugs were dissimilar; they resembled each other in the patients of their effect as a function of the course of administration into the cells infected with the virus. Both preparations inhibited the synthesis of virus specific proteins exhibiting distinct effects under conditions of preliminary or immediate administration following the infection. At the same time, the inhibitory properties of remantadine were maintained at the subsequent period after infection; these were not observed in the amantadine treatment.

[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.

[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.

[Inhibitory effect of alpha-methyl-1-adamantane methylamine hydrochloride (rimantadine) on RNA-dependent RNA polymerase induction in culture of cells, infected with influenza virus]. / Ingibiruiushchee deistvie solianokislogo al'fa-metil-1-adamantanmetilamina (rimantadina) na induktsiiu RNK-zavisimoi RNK-polimerazy v kul'ture kletok, infitsirovannykh virusom grilla

An anti-influenza preparation, rimantadine (alpha-methyl-1-adamantane methylamine hydrochloride) at concentrations of 10--25 mkg/ml depresses the RNA-dependent RNA polymerase induction in a culture of cells infected with influenza virus (fowl plague virus). The inhibitory effect is also observed 2 hours following cell infection. In vitro studies have demonstrated that rimantadine has no effect on the activity of virus-induced RNA-dependent RNA polymerase, as well as on that of RNA-dependent RNA polymerase associated with virus particles.