Enteroviruses identifications and differentiation on the basis of the selective group--specific inhibitory effect of chemical compounds.

Two new enteroviruses (EV) inhibitors with the selective group-specific effect were detected and studied representing the products of the original chemical synthesis. One of them--nifan (arylfuran derivative) inhibits poliomyelitis virus replication, the other one--belvtazide (synchonic acid derivative) blocks non-poliomyelitis EV (ECHO and Coxsackie B) replication. The study of the reference strains of poliomyelitis virus type 1-3, twenty-three ECHO virus types (from the 1st to the 33rd), Coxsackie B virus type 1-6 and 288 primary EV isolates did not reveal type or strain specific variability in the inhibitors effect. Nifan and belvtazide supress the replication of both EV monostrains and their mixtures. The isolates of mixed nature are inhibited by the mixture nifan + belvtazide. At the same time neither separate chemicals nor their blend affects viruses from other families (Adenoviridae, Orthomyxoviridae, Herpesviridae etc.). The mechanism of nifan and belvtazide action is intracellular EV replication inhibition (they do not affect the process of virus adsorption and penetration into the cell), suppression of de novo virus synthesis by 7.0-2.25 lg (tissue culture infective dose 50 per cent) TCID50/ml and of virus-induced RNA synthesis. The drugs feature is high selectivity (90-91%) regarding RNA polioviruses (nifan) and RNA non-poliomyelitis EV (belvtazide). Nifan and belvtazide antiviral effect selectivity allows unknown cytopathic agents (CPA) belonging to the EV to be established with the high degree (over 98%) of reproducibility at the stage of primary identification with the differentiation of poliomyelitis and non-poliomyelitis viruses.

[The efficacy of an antiviral factor obtained from infected chick embryo fibroblasts in an experimental herpetic infection]. / Effektivnost' antivirusnogo faktora, poluchaemogo iz infitsirovannykh fibroblastov kurinogo émbriona, pri éksperimental'noi gerpeticheskoi infektsii.

Treatment of mice with an antiviral factor obtained from the culture medium of infected chick embryo fibroblasts protected them against lethal meningoencephalitis caused by herpes simplex virus. The degree of protection varied from 50 to 75% depending on the virus dose, the route of infection, and the mode of the antiviral factor application.

[Dyslipidemia and an elevated lipid level in the cells in experimental herpetic infection and their correction with antiviral chemotherapeutic agents]. / Dislipidemiia, povyshennoe soderzhanie v kletkakh lipidov pri éksperimental'noi gerpeticheskoi infektsii i ikh korrektsiia antivirusnymi khimiopreparatami.

The influence of herpes simplex virus on lipid exchange and accumulation by blood vessels cells was studied. In acute herpes infection in rabbits, typical dyslipidemia characterised by a rise in the content of total cholesterol, low and very low density lipoprotein cholesterol and triglycerides in the absence of manifest changes in concentration of high density lipoprotein was detected. HSV infection of smooth muscle cell culture of human embryo aorta was accompanied by increased accumulation of free lipids in the cells. The use of antiherpetic preparations during the infection led to correction of the lipid spectrum of the infected animals and was accompanied by normalization of intracellular lipid contents. A possible pathogenetic role of HSV in atherogenesis which may be connected with at least two processes: the development of lipidemic disturbances and formation of pathologic lipid depot in the arterial wall, is discussed.

[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.

[Dyslipidemia in herpetic infection]. / Dislipidemiia pri gerpeticheskoi infektsii.

Herpes ophthalmicus (HO) patients were examined for lipid spectrum of the serum. The tests revealed dyslipidemia (DLE) with a distinctive rise in the levels of total cholesterol (CS), alpha-CS and beta-CS. The severity of the lipidemic shifts correlated with that of the infection. DLE was more marked in recurrent HO. Clinical evidence was consistent with experimental findings. In rabbit models, herpetic keratoconjunctivitis was characterized by pronounced lipidemic alterations correctable with antiherpetic drug furavir. The results are discussed in terms of herpetic infection pathogenesis and its role in the development of atherosclerosis.

[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.

[Experience in the use of chemical compounds for the primary identification and differentiation of enteroviruses]. / Opyt ispol'zovaniia khimicheskikh soedinenii dlia pervichnoi identifikatsii i differentsiatsii énterovirusov.

Data on the usage of chemical inhibitors nifan and belvtazid, which possess a selective and antienteroviral effect, in the primary identification of enteroviruses and their differentiation into polio- and non-poliomyelytic ones isolated from human clinical materials or the environment by using the cell culture are presented in the article. The method is recommended for the practical use by the virology service in the diagnostics of enteroviral infections and in the identification of cytopathic agents isolated from the enviroment.

[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.