[A study of the antiherpetic activity of the chaga mushroom (Inonotus obliquus) extracts in the Vero cells infected with the herpes simplex virus].

The chaga mushroom (Inonotus obliquus) contains a wide range of excellent bioactive compounds. However, limited information exists on the antiviral activity of the compounds extracted from chaga. A number of subfractions of chaga were obtained using different solvents and different procedures. The subfractions of chaga extracted with water, alcohol, alkali were tested for their toxicity for the Vero cell culture and antiviral effect in the Vero cells infected with the Herpes simplex virus (HSV), Type 1. It was shown that most of the subfractions were not toxic for the Vero cells and had protective effect on the Vero cells infected with HSV. The subfraction IV in the concentration 5 microg/ml protected the Vero cells from cytodestructive action of HSV and no viral DNA was detected in infected cells treated with chaga extracts. Best protective effect was observed when compound was added before or within one hour after the Vero cells were infected with HSV.

[The interferon-induced and antiviral activities of dipeptides].

Five phosphodipeptides were synthesized; two of them (H-Lys-Ala(P) and H-Pro-Ala(P) had interferon-induced activity. These dipeptides at millimolar concentrations (10(-4)) and 10(-5) M) induced the synthesis of late (40-hour) interferon in human peripheral blood lymphocytes. The dipeptides H-Lys-Ala(P) and H-Pro-Ala(P) showed a protective antiviral activity in in vivo studies when singly intraperitoneally administered to mice 2 hours before inoculation with murine encephalomyocarditis virus.

[Antiviral activity of extracts of basidiomycetes and humic compounds substances against Human Immunodeficiency Virus (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus 1) and Herpes Simplex Virus (Herpesviridae: Simplexvirus: Human alphaherpesvirus 1)].

INTRODUCTION: One of the most urgent problem of modern medicine is the fight against the disease caused by the Human Immunodeficiency Virus (HIV) - HIV infection. The chemical compounds have improved the situation for infected people, but they are toxic, disrupt the metabolism and cannot eliminate the integrated virus from the body. The emergence of resistant HIV strains makes these treatments ineffective. Often, the death of HIV-infected people occurs as a result of the development of opportunistic infections caused by viruses of the Herpesviridae family. Therefore, the search for new therapeutic and preventive drugs that are less toxic and active against several viruses at the same time is relevant. Basidiomycetes, higher fungi, are a source of medicinal compounds that have antimicrobial properties, as well as antiviral ones. Humic compounds (HS) of various nature also have antiviral activity.The aim of the study was to obtain nontoxic compounds from the basidiomycete Inonotus obliquus and humic compounds from brown coals and to test their activity against viruses that are pathogenic to humans: HIV and Herpes Simplex Virus (HSV). MATERIAL AND METHODS: The antiviral activity of melanin extracts obtained from the culture of the chaga fungus Inonotus obliquus and HS from the brown coal of the Kansko-Achinsk Deposit was studied using a model of MT-4 lymphoblastoid cells infected with HIV type 1 (HIV-1) strains and a monolayer culture of Vero cells infected with HSV type 1 (HSV-1) using virological and statistical research methods. RESULTS AND DISCUSSION: It was found that all the studied compounds did not have a cytotoxic effect on cells at a concentration of 100 mcg/ml. It was shown that extracts of basidiomycetes and HS have antiviral activity against HIV-1 and HSV-1. EC 50 (50%-effective concentration) for HIV-1 was 3.7-5.0 mcg/ml, selectivity index 28-35. Antiherpetic activity was detected at a dose of 50-100 mcg/ml. The antiviral effectiveness of melanin compounds was established both in the «preventive¼ (2 hours before cell infection) and in the «therapeutic¼ regimen of drug administration, both for HIV-1 and HSV-1. The presence of antiviral activity of melanin and HS in relation to the RNA-containing HIV-1 virus and DNA-containing HSV-1 virus in our study coincides with the results of a number of authors in relation to influenza viruses, herpes virus, HIV, hepatitis B virus, Coxsackievirus, smallpox vaccine virus, which suggests that the type of nucleic acid in the virus does not play a fundamental role in the antiviral action of these drugs. It is also clear that HS is effective against both enveloped and non-enveloped viruses. CONCLUSION: In general, it can be concluded that melanin and humic compounds are characterized by low toxicity in the presence of both virucidal and antiviral activity. This allows us to consider the studied compounds as the basis for creating safe medicines that are effective against pathogens of various viral infections.

[Fullevir: in vitro and in vivo antiherpetic activity].

The antiherpetic properties of a fullerene derivative with aminocaproic acid (manufactured by Intelfarm Co. as Fullevir) were studied in in vitro (in sensitive cell cultures) and in vivo (on a murine model of experimental herpetic encephalitis) experiments. Fullevir was found to protect tissue culture cells from the cytodestructive action of herpes simplex virus type 1. It was estimated that ED50 = 5.3 microg/ml and ED90 = 29.1 microg/ml. The agent was most effective when it was administered before and 30 minutes after cell culture infection. The in vivo study established that Fullevir showed a significant protective effect in experimental herpetic encephalitis. The protection rates were 29.8% and 41.0% with the total doses of Fullevir of 500 mg/kg (p < 0.007) and 1000 mg/kg (p < 0.004), respectively. Thus, the in vitro and in vivo studies demonstrated the antiherpetic effect of a fullerene-aminocaproic acid complex (1-hydrofullereneaminocaproic acid, sodium salt) having the trade name Fullevir.

[Interferon-inducing properties of dry birch bark extract and its effect on experimental infection caused by hepatitis C virus].

The interferon-inducing activity of dry birch bark extract containing betulin and its effect on hepatitis C virus (HCV)-induced infection were studied in the cultured cells. All samples of the extract induced increased interferon (IFN) production when it was orally and intraperitoneally administered. The dose-dependence of the production of IFN showed a direct relation of the extract to interferon induction. There is strong evidence for that the extract can decrease the antigenic and infective activity of HCV in both in vitro experiments and HCV-induced infection in mice. The preventive effect of the extract was found in both the HCV-infected cell cultures and the HCV-infected mice.

Experimental study of the reproduction of Karshi virus (Togaviridae, flavivirus) in some species of mosquitoes and ticks.

The strain Kaz-816 of Karshi virus was isolated in 1976 from H. asiaticum ticks collected in the North of Central Asia (Alma-Ata region of the Kazakh Soviet Socialist Republic). Both ticks and mosquitoes can be vectors of Karshi virus as proved experimentally by reproduction of the virus in Hyalomma asiaticum and Dermacentor daghestanicus ticks and Culex pipiens molestus, Anopheles atroparvus an Aedes aegypti mosquitoes as well as by transmission to newborn mice by the bite of infected mosquitoes.

[Preparation of rat ascitic fluids immune to the Sakhalin group viruses (fam. Bunyaviridae)]. / Poluchenie immunnykh astsiticheskikh zhidkostei krys k virusam gruppi Sakahlin (Sem. Bun'iaviride).

A method for preparation of rat immune ascitic fluids (IAF) to arboviruses of the Sakhalin group (the family Bunyaviridae) is described. These IAFs were 2-8-fold more active in the CFT and AGDP tests than similar preparations produced in white mice. Besides, this method is more economic.

[Etiology of Karelia fever--a new arbovirus infection]. / Etiologiia karel'skoi likhoradki--novoi arbovirusnoi infektsii.

In August-September 1981, in some areas of Karelia (on the border of northern and middle taiga) there occurred diseases with signs of fever, rash, and arthralgia developing in some patients into a chronic condition. Examinations of paired sera from patients with the acute disease and from convalescents using a set of Toga- and Bunya-viruses showed the etiology of the disease to be associated with a virus from the Togaviridae family, genus Alphavirus, of the antigenic Sindbis complex.

[Sakhalin antigenic group (Bunyaviridae family)]. / Antigennaia gruppa Sakhalin (semeistvo Bunyaviridae).

Serological study of viruses belonging to the Sakhalin group showed Paramushir virus isolated in the USSR and Avalon virus isolated in Canada to be identical in all the tests used. The data on the cultural properties of the Sakhalin group viruses, the virions buoyant densities in sucrose gradient, the data on thermal sensitivity and UV inactivation of the viruses, on their morphology and morphogenesis are presented.

[Antiviral and anti-stress activity of the gamma-L-glutamyl-histamine and its derivatives]. / Protivovirusnaia i antistressornaia aktivnost' gamma-L-glutamilgistamina i ego analogov.

Effect of gamma-L-glutamylhistamine gamma-L-Glu-HA and some of its derivatives on the state of nonspecific resistance and antiviral activity was studied using experimental models of influenza virus and herpes simplex virus infections. Activities of natural killer (NK) cells and interferon (IFN) system were measured. The model of physical-emotional stress in mice was used. It was shown that the gamma-L-Glu-HA derivative II can prevent totally or substantially a decrease in the NK activity. This agent also prevents inhibition of synthesis of alpha- and gamma-IFN during the post-stress period. The gamma-L-Glu-HA derivatives II, III, and VII increased the mice resistance to influenza virus type A/Aichi at low infection dose (10LD50). The derivative II showed its protective effect even at high dose of pathogen (100LD50). However, this gamma-L-Glu-HA derivative was virtually ineffective under harsh experimental conditions. Thus, a number of gamma-L-Glu-HA derivatives tested in this work demonstrated immunomodulation activity. These agents were able to normalize parameters of nonspecific immunity. They exerted a pronounced antiviral effect against influenza virus but were virtually ineffective against encephalitis in mice caused by herpes simplex virus, type 1. Of all tested agents, gamma-L-Glu-HA derivative II was found to be the most promising.

[Activity of "Ferrovir" preparation towards RNA and DNA viruses]. / Aktivnost' preparata "Ferrovir" v otnoshenii RNK- i DNK- soderzhashchikh virusov.

Ferrovir (trivalent iron in complex with native sturgeon milt DNA) is nontoxic, its 50% inhibiting concentration (IC50) is at least 4000 micrograms/ml, 90% effective concentration (EC90) towards HIV-1 is 800 micrograms/ml. These effects do not depend on the cell culture or individual biological characteristics and subtypes of 7 strains of HIV-1 used in our study. The chemotherapeutic index of the drug is more than 20. Combined therapy with ferrovir and retrovir had an additive antiviral effect. Ferrovir reduced the titer of human CMV in fibroblast culture by 1-2 Ig TCD50. Ferrovir protected mice after intracerebral inoculation with lethal herpes simplex virus (type 1) (survival 33.7%, protection 27.1%, which is close to the reference group treated with zovirax). These facts evidence antiviral activity of ferrovir towards RNA and DNA viruses and prompt further study of this drug with the aim of its clinical application.

[The circulation of viruses of the California encephalitis and Bunyamwera groups (Bunyaviridae, Bunyavirus) on the northeastern Russian plain]. / Tsirkuliatsiia virusov kompleksov Kaliforniiskogo éntsefalita i Bun'iamvera (Bunyaviridae, Bunyavirus) na severo-vostoke Russkoi ravniny.

In the Komi ASSR, 102.2 thousand mosquitoes, 207 small mammals, 1487 blood serum specimens from people, 793 cow blood sera, 140 blood serum specimens from reindeer were collected in June-August, 1988. Twenty seven virus strains isolated from mosquitoes were classified into Bunyaviridae family according to the data of electron microscopic studies. Identification of the isolates by CFT and IFA showed 18 of the strains to belong to California encephalitis complex and 9 to Bunyamwera complex. Serological studies by neutralization test demonstrates a high frequency of contact of the human population and domestic animals with viruses of the California complex practically in the entire study area: an average of 45% among human subjects, 48% among cattle and 33% among reindeer. Such high values of the immune portions indicate the activity of the discovered natural foci of this complex. The results for Batai virus from the Bunyamwera complex do not indicate its high activity: approximately 2% of positive findings in human subjects and about 4% in the cattle. The results permit a prognosis of California encephalitis and Bunyamwera complex viruses spread in the northern part of Western Siberia.

[The isolation of tick-borne encephalitis virus strains and the determination of the scope of immune stratification among the population and the domestic animals on the northern Russian plain]. / Izoliatsiia shtammov virusa kleshchevogo éntsefalita i opredelenie velichiny immunnoi prosloiki sredi naseleniia i domashnykh zhivotnykh na severe Russkoi ravniny.

Between 1986 and 1987 the authors conducted virological survey of 689 Ixodes persulcatus and 420 mouse-like and insectivorous rodents at the territory of Arkhangelsk Province and the Republic of Komi. A total of 8 strains of tick-borne encephalitis virus were isolated. Out of them 3 strains were isolated from small mammalians (2 from Clethrionomys glareolus, 1 from Microtus oeconomus) at the southeastern areas of Arkhangelsk Province within the middle taiga subarea, 5 strains were isolated from I. persulcatus (the rate of infection was 1.25 per cent) gathered in the southeastern Komi within the southern margins of the middle taiga subarea. PHAT investigation of the sera (2064 human, 656 cow and 171 dear specimens) evidenced almost the absence of immunity among the studied populations of the tundra and forest tundra zones. Certain positive samples observed in the northern taiga region could be explained by the infection gained in areas situated more to the south. Among the middle taiga human populations the immunity reached 4.9 per cent.