[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.

[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.

[Viral sorption on polyaniline, carbon nanotubes and their based nanocomposites].

The paper gives data on the sorption of influenza virus pandemic strain A/IIV-Moscow/01/2009 (H1N1)swl, avian influenza viruses with A/H5 and A/H7 hemagglutinin, poliomyelitis virus, and T4-D bacteriophage on polyaniline sorbents, carbon nanotubes, and their based nanocomposites. The sorption of viruses occurred in different solutions at 4-37 degrees C during 15 min or more. The rate of viral sorption depended on the structure of sorbents.

[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.

[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.

[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.

[Effect of amyxin--a domestic analog of tilorone--on characteristics of interferon and immune status of man]. / Vliianie amiksina--otechestvennogo analoga tilorona--na pokazateli interferonovogo i immunnogo statusa cheloveka.

The influence of amyxin, the Russian oral analog of tilorone, on the human interferon and immune status has been evaluated. As revealed by this investigation the administration of amyxin has produced a rise in the content of serum interferon, an increase in the capacity of leukocytes and lymphocytes for synthesizing alpha- and gamma-interferon, the activation of NK and phagocytizing cells of peripheral blood. No essential influence of amyxin on the amount of B and T lymphocytes, their subpopulations and the levels of the main classes of immunoglobulins has been established.

[Cytokines in viral infections]. / Tsitokiny pri virusnykh infektsiiakh.

The role of cytokines and chemokines in viral replication and antiviral immunity is discussed. Some viruses may have genes that mimic the host genes (cytokines or cytokine receptors) and their functioning may inhibit the synthesis or processing of cell proteins important for defense. Some of host cytokines may be involved in the pathogenesis of viral infection (HIV, herpes virus, cytomegalovirus, and some others).

[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.

[Arbidole--a new drug for prevention of influenza and acute viral respiratory infections in children]. / Arbidol--novoe sredstvo dlia profilaktiki grippa i ostrykh respiratornykh virusnykh infektsii u detei.

The antiviral drug arbidole reduces influenza and acute respiratory diseases (ARD) in children by 1.5-2 times when given in a dose of 0.1-0.2 g 2-3 or 5 times a week, by making influenza and ARD milder and decreasing their duration by 1.4-2.8 days. Unified regimens for prophylactic use of arbidole in influenza and ARD in children and adults are proposed.

[Clinical trials of recombinant gamma-interferon. Circulating interferon and the 2,5-oligoadenylate synthetase activity after intramuscular and inhalation administrations]. / Klinicheskie ispytaniia rekombinantnogo gamma-interferona. Tsirkuliruiushchii interferon i aktivnost' fermentov 2,5-oligoadenilatsintetazy pri vnutrimyshechnom i ingaliatsionnom vvedeniiakh.

It was shown that human recombinant gamma IFN given to volunteers intramuscularly (90 x 10(3) IU) and by inhalation (120 x 10(3) IU) induced 5-10-fold increase circulating IFN (up to 40-60 IU/ml); the activities of 2,5-oligoadenylate synthetase increased 1.5-2 fold and protein kinase of lymphocytes--3-5-fold. The repeated doses of gamma IFN at 12-15-hour intervals maintained a relatively stable IFN status, the inhalatory route of application being more effective. Convalescents after influenza different from healthy donors by a higher level of serum interferon and activity of 2.5-oligoadenylate synthetase but the activity of protein kinase was lowered in lymphocytes and plasma. The side effects induced by IFN administration were more marked only after intramuscular injections of 90 10 IU and were absent after inhalation of IFN (120,000 IU).

[The inhibiting action of interferon inducers on the multiplication of the human immunodeficiency virus]. / Ingibiruiushchee deistvie induktorov interferona na razmnozhenie virusa immunodefitsita cheloveka.

High molecular natural (ridostin and larifan) and synthetic (camedon) interferon inducers inhibited HIV-1 replication in MT-4 and CEM cultures when administered simultaneously with the inoculum. The effect of interferon inducers was comparable with that of azidothymidine in concentrations providing cell protection. The degree of culture protection determined by the number of viable and antigen-containing cells was approximately similar for strain 899A and freshly isolated IV39. No significant difference in the efficacy of the preparations in the two different cell cultures. MT-4 and CEM, was observed. It may be assumed that the antiviral effect of the interferon inducers under study will depend little on the type of cell culture.

[Experience with the combined treatment of recurrent herpes using larifan and a herpetic vaccine]. / Opyt kombinirovannogo lecheniia retsidiviruiushchego gerpesa larifanom i gerpeticheskoi vaktsinoi.

Interferon inductor larifan used parenterally was combined with herpetic vaccine to treat severe recurrent herpes in 32 patients. This combination therapy started at initiation of herpetic infection activation and resulted in amelioration of the clinical symptoms of the recurrence, a more favourable course of the disease due to stimulation of the interferon system and natural killer activity. In combination the above modalities proved more effective than in monotherapy.

[Evaluation of 2,5-oligoadenylate synthetase and protein kinase activities in clinical studies of larifan and recombinant interferon alpha in volunteers]. / Otsenka aktivnosti 2,5-oligoadenilatsintetazy i proteinkinazy pri klinicheskikh ispytaniiakh larifana i rekombinantnogo alfa2 - interferona na dobrovol'tsakh.

The activity of the interferon-dependent enzymes: 2',5'-oligoadenylate synthetase and protein kinase was determined in blood specimens of volunteers in the clinical trials on reaferon (recombinant alpha 2-interferon) and larifan (replicate RNA of phage f2). It was shown that the preparations increased the activity of 2',5'-oligoadenylate synthetase in the lymphocytes and protein kinase in the plasma of 60 to 70 per cent of the volunteers. The increase in the 2',5'-oligoadenylate synthetase activity did not always correlate with the increase in the interferon content in the serum and was sometimes observed in the absence of the interferon. Marked individual variations in the activity of the enzymes were detected in the volunteers before and after administration of the preparations. The plasma kinase activated by reaferon and larifan phosphorylated proteins with molecular weights of 72 and 30 kD and histones. The effect of reaferon and larifan on the lymphocyte protein kinase activity was determined for the first time. There was a decrease in the enzyme activity under the effect of reaferon which increased after its repeated injections. Unlike the effect of larifan, the inhibitory effect of reaferon was transient. Afterwards, it appeared to be accompanied by a significant increase in the activity of protein kinase in 70 per cent of the volunteers. The dynamics of the changes in the activity of the plasma and lymphocyte protein kinases did not coincide.

[Effect of double-stranded RNA and interferon type I on reproduction of cytomegalovirus in human fibroblasts]. / Effekt dvuspiral'nykh RNK i interferonov tipa I na reproduktsiiu tsitomegalovirusa v fibroblastakh cheloveka.

Double-stranded RNAs (dsRNA) - larifan and ridostin, and recombinant interferons-alpha-2 and beta-1, manufactured in the USSR, inhibited the reproduction of CMV in cell culture. Antiviral effect depended on concentration of preparations, time of administration and m. o. i. DEAE-dextran enhances antiviral effect dsRNA. DsRNA and interferons added to cells infected with CMV at high m. o. i. enhance the viral reproduction. Among studied preparations highest antiviral effect was shown by natural leucocyte interferon (Egis). It was 10 times more active, than recombinant IFNs and in concentration of 1000 U/ml was comparable to activity of larifan (200 mg/ml).

[Enzyme activity of interferon system in virus diseases]. / Aktivnost' fermentov sistemy interferona pri virusnykh zabolevaniiakh.

The enzymes activities of interferon system at viral infections of different etiology/influenza, parainfluenza, hepatitis B with delta infection and urticaria chronica with respiratory and herpes infection/has been studied and evaluation of the noted changes in the enzymes activity is discussed. It is shown that the same pathological changes in enzymes activities of interferon system were observed at different viral infections.