[Activity of the inositol-containing phospholipid dimer analogues against human immunodeficiency virus].

For the purpose of finding effective inhibitors of virus adsorption the series of inositol-containing phospholipid dimer analogues were previously synthesized. In the present work, the antiretroviral activity of these compounds against HIV-1 was demonstrated on the model of cells infected with the virus. The highest effect was found in the case of dimer poliol 5, EC50 (50%-effective concentration) was 3.9 microg/ml. The development of new polyanionic compounds, which can interfere with early steps of the virus life cycle, is a promising addition to the antiretroviral therapy based on the virus enzyme inhibitors.

[Synthesis, properties and anti-HIV activity of novel lipophilic 3'-azido-3'-deoxythymidine conjugates containing functional phosphoric linkages].

One of the approaches to enhance bioavailability of nucleoside reverse transcriptase HIV inhibitors consists in design of their prodrugs based on 1,3-diacylglycerols, which may simulate nature lipids metabolic pathways promoting the improvement of drug delivery to the target cells. Glycerolipidic AZT conjugates with different functional phosphoric centers were synthesized by H-phosphonate technique in the present work. Study of prepared prodrugs sensibility to the chemical and enzymatic hydrolysis (in buffer solution and under the influence of pancreatic lipase) and also study of their anti-HIV activity on the T-lymphoid human MT-4 cells in regarding to virus HIV-1(899A) strain were carried out.

[Antiviral and virucidal activity of sodium deoxyribonucleate and its complex with iron against viruses of different kingdoms and families].

INTRODUCTION: The urgent problem of modern medicine is the fight against acute respiratory viral infections (ARVI). To combat ARVI, drugs of wide antiviral potency are needed, as well as immunomodulating drugs. Such antiviral and immunomodulatory effects has sodium deoxyribonucleate (DNA-Na) and its complex with iron (DNA-Na-Fe) developed on the basis of double-stranded DNA of natural origin. AIM OF THE STUDY: To assess antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against viruses of different kingdoms and families. MATERIALS AND METHODS: Antiviral and virucidal activity of DNA-Na and DNA-Na-Fe was assessed in cell cultures infected with viruses. RESULTS AND DISCUSSION: DNA-Na and DNA-Na-Fe had antiviral activity against adenovirus at concentrations of 2501000 mcg/ml. Antiviral effect of both drugs was not detected in case of poliovirus. DNA-Na and DNA-Na-Fe had antiviral activity against coronavirus in all administration schemes. EC50 for DNA-Na ~ 2500 mcg/ml, for DNA-Na-Fe ~ 1000 mcg/ml. In cells treated with DNA-Na-Fe, secretion of following proinflammatory cytokines was detected: Interleukin (IL) 1, IL-2, IL-6, IL-18, interferon- (IFN-), IFN-, as well as anti-inflammatory cytokines: IL-4, IL-10, antagonist of IL-1 receptor. Evidently, DNA-Na and DNA-Na-Fe have antiviral effect, but mechanism of action does not seem to be associated with specific effect on viral replication. Presence of virucidal activity of drugs against representatives of Coronaviridae, Adenoviridae, Picornaviridae, Retroviridae, Herpesviridae in vitro test in range of 1.03.0 lg TCID50 was identified. CONCLUSION: Presence of simultaneous antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against adeno- and coronaviruses shows their prospects for prevention and treatment of ARVI.

[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.

[The antiretroviral agent Fullevir].

The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

CYTOTOXIC PROPERTIES OF TRITERPENE SAPONIN TAUROSID SX1 AND ITS EFFECT ON HUMAN IMMUNODEFICIENCY VIRUS AND INFLUENZA VIRUS INFECTION IN MICE.

Triterpene saponin Taurosid Sx1 purified from leaves of the plant Crimean Ivy Hedera taurica Carr. (Araliaceae) was evaluated for its cytotoxic activity against lymphoblastoid cell lines MT-4, Jurkat-tat, U937, and human peripheral blood monocytes. The ability of saponin to influence HIV-1 replication was studied as well. In addition, the ability of Taurosid Sx1 to increase survival of mice infected with influenza virus А/WSN/1/33(H1N1) and its capacity for strengthening the immune responses in mice immunized with the influenza vaccine Grippol® have been studied. Taurosid Sx1 has been shown to inhibit MT-4 cell line at 25 µg ml-1 concentration, IC50 33,3 µmol l-1 (MTT assay). The saponin concentration of 5 µg ml-1 was non-toxic for all the cell lines studied and demonstrated a moderate inhibitory effect on HIV p24 production in Jurkat-tat cells. In the lower concentrations Taurosid Sx1 did not stimulate HIV p24 production. It was shown that oral administration of 200 µg Taurosid Sx1 to the influenza virus infected mice caused 1.5-fold increase in their survival. Taurosid Sx1 given orally amplified immunopotentiating ability of an intramusculary administered subunit influenza vaccine. Antibody production was significantly higher in animals fed Taurosid Sx1 after primary or secondary immunizatuion. In mice given 2 doses of vaccine, from 1 to 3 weeks apart, feeding 200 µg saponin resulted in 2 to 10-fold enhancement in production of anti-H1, anti-H3, and anti-inluenza type B hemagglutinin antibodies. Thus, Taurosid Sx1 can be considered as low-toxic promising immunopotentiating agent uncapable of enhancing HIV-1 replication.

[Sensitivity of Russian HIV-1 isolates to anti-HIV agents]. / Chuvstvitel'nost' k anti-VICh-preparatam izoliatov VICh-1, vydelennykh na territorii Rossii.

HIV strains isolated from HIV patients hospitalized at the Central Research Institute of Epidemiology in 1991-1993 are analyzed. HIV-1 strains isolated at different stages of the illness were referred to subtypes A and B. The biological properties of the isolates of both subtypes were virtually the same. The majority of the isolated HIV-1 strains were relatively resistant to azidothymidin, no matter whether the patients were previously treated with this drug or not. Study of strains repeatedly isolated from the same patients showed an increase of the cytodestructive characteristics of the isolates. Strains isolated from the same epidemiological chain were characterized by the same properties and sensitivity to the tested antiHIV agents. The resistance of the virus to antiHIV drugs with different mechanisms of action may be an indicator of the terminal stage of the illness.