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The peculiarities of the spread of vaccine-like viruses first revealed more than 50 years ago in the area of the South America was discussed. These viruses cause infective episodes among milk cattle and caretaking personnel. Cancellation of the smallpox vaccination in 1980 resulted in a decrease in the community immunity and increased the risks of human infection. This circumstance makes it necessary to activate monitoring of the properties of the vaccine-like viruses, the circle of hosts and possible changes in the pathogenicity for humans.

The efficacy of Triazavirin against the tick-borne encephalitis virus was estimated in the sensitive cell culture vs. the active drug Ribavirin. In a concentration of 128 mcg/ml Triazavirin was shown active in inhibition of the tick-borne encephalitis virus reproduction (strain Sofiin) by accumulation in the SKEV cell culture.

Features of spread of cowpox in the contemporary conditions are examined. A decrease of population immunity to pox in the population of Russia caused by cancellation of pox immunization, hidden circulation of cowpox virus in various species of rodents, as well as lack of vigilance to pathogenic orthopoxviurses in healthcare workers were noted to create the real preconditions for the emergence of infection of humans caused by cowpox virus. Thereby presence of means of express laboratory diagnostics of cowpox and means of effective medical protection for the prevention of development of this disease in the population of Russia becomes an actual necessity.

Aim: Study of immunogenicity and protective efficacy of a novel inactivated vaccine with chitosan against influenza A/H1N1/2009., Materials and Methods: Influenza virus A/California/7/2009 (H1N1) strain was used in the study. Mice were immunized twice (21 day interval) with experimental samples of inactivated influenza vaccine: No. 1--without the addition of chitosan, No. 2--with addition of chitosan. The blood was obtained 21 days after the first and 10 days after the second immunization with the vaccines and was treated with RDE. Antibody levels were evaluated in HI reaction., Results: HI reaction method showed that antibody titers induced after immunization of vaccine No. 2 were higher than those induced after immunization with vaccine No. 1. Evaluation of protective efficacy of the vaccines against an experimental form of influenza infection in mice showed that after immunization with vaccine that does not contain chitosan the level of virus accumulation does not differ from the control statistically significantly (p < or = 0.05), at the same time the level of virus accumulation in the lungs of infected animals immunized with chitosan containing vaccine significantly (significantly with 95% probability) decreased by an average 3.01g when compared with control., Conclusion: Comparative analysis of immunogenicity and protective efficacy of experimental samples of inactivated influenza vaccine against influenza A/H 1N1/2009 showed that the vaccine with the addition of chitosan stimulates the formation of a higher immune response and promotes a more significant suppression of influenza A infectious agent reproduction in the lung target-organ.

The study of the toxicity of triazavirin, a new antiinfluenza agent, showed that the maximum concentration of the drug, inducing no microscopically visible changes in the structure of the monolayer and the cells of the MDCK and SKEV cell cultures, was 128 and 100 mcg/ml respectively. The maximum drug dose for single intraperitoneal administration inducing no signs of acute intoxication in albino mice weighing 10-12 g was 1000 mg/kg. In investigation of the chronic toxicity it was shown that oral administration of the drug (by 0.05 ml) to the albino mice in a dose of 200 mg/kg (maximum possible concentration by the solubility) daily for 10 days was well tolerated by the laboratory animals. The maximum tolerable dose of triazavirin for the albino mice was > or = 200 mg/kg.

Therapeutic activity of Triazavirin against experimental influenza A was studied on albino mice intranazally infected with influenza virus A/Chicken/Kurgan/Russia/02/05 (H5N1) vs. reference drugs (Oseltamivir, Remantadin and Arbidol). The study showed that in a therapeutic dose of 1 mg/kg Triazavirin was efficient in protection of the animals from death. Its protective therapeutic efficacy (36.7+/-1.7%) was close to that of Oseltamivir (50.0+/-0.0%), comparable with that of Remantadin (38.3+/-1.7%) and higher than that of Arbidol (11.7+/-1.7%). During the whole observation period (up to the terminal phase) Triazavirin inhibited the influenza virus A accumulation in the lungs of the infected albino mice by more than 3 lg.

Foreign experience with empirical management of severe acute respiratory syndrome (SARS) due to coronavirus, genotype IV is described. It is indicated that the data on the efficacy of ribavirin with respect to SARS in the patients are contradictory. The efficacy of two chemotherapeutics, i. e. lopinavir and ritonavir used in the SARS foci is confirmed. The drugs are at present applicable all over the world in retrovirus therapy of HIV infected subjects. The search for efficient Russian unspecific medicines for control of SARS is actual.

The results of the in vitro studies on the efficacy of medical nonspecific protective agents from various pharmacological groups showed that some drugs, such as velferon, alferon, betaferon, ribavirin and lopinavir were active against TOPC virus, that permitted to recommend them for estimation of their activity on laboratory animals. The data on the in vivo activity of pharmacological drugs with respect to TOPC virus are rather scanty and it is difficult to predetermine their efficacy. The danger of TOPC virus latent circulation among wild animals in China requires research of new efficient medical agents for protection of the people from the pathogen in the Russian Federation.

Analysis of the efficacy of Grippferon vs. the reference drugs Realdiron and Reaferon-EC against the influenza virus A(H1N1)/2009 in susceptible static cell cultures showed that in the concentrations tested it was efficient in inhibition of the virus cytopathic activity and generation of specific hemagglutinin.

The experimental study of the Ingavirin efficacy against the influenza virus A (H5N1) on intranasally-infected albino mice vs. Tamiflue and Arbidol showed that when used for the prophylaxis, urgent prophylaxis and therapy it was effective in the protectiom of the animals from death. The efficient dose for the prophylaxis of the influenza infection was 5 mg/kg (protective efficacy of 46.7%) and for the urgent prophylaxis and therapy it was 15 mg/kg (protective efficacy of 40.0 and 35.0% respectively).

The experimental study of the prophylactic efficacy of Triazaverin against the experimental form of the influenza virus A (H5N1) on albino mice intranasally infected with the influenza virus A/Chicken/Kurgan/Russia/02/05 vs. the reference drugs Tamiflu, Remantadin and Arbidol showed that in doses of 1 to 100 mg/kg it was efficient in the animal protection from death. The drug was also efficient in the urgent prophylaxis. Triazaverin effectively inhibited the influenza A virus multiplication in the lungs of the albino mice.

The virucide activity of Monclavit-1 against the influenza virus A/Chicken/Kurgan/2/Russia/05 (H5N1) was investigated in the MDCK cell culture. It was shown that at a temperature of 14.0 +/- 1.0 degrees C Monclavit-1 in a 20-fold dilution within an hour inactivated the cytopathic activity of the virus and the specific hemagglutinin generation by 100 and 87.5% respectively. In a 40-fold dilution it inactivated at the average by 50% both the cytopathic activity and the specific hemagglutinin generation. In an 80-fold dilution it inactivated the cytopathic activity at the average by 20%. In a 160-fold dilution it did not inactivate the pathogen. At a temperature of 25.0 +/- 1.0 degrees C Monclavit-1 inactivated the influenza virus A/Chicken/Kurgan/2/Russia/05 (H5N1) by 90.0% only in the highest concentration.

Efficacy of arbidol and ridostin in cupping postvaccinal complications due to variolation was studied by the clinico-virological, hematological and biochemical indices and it was shown that arbidol was efficient in cupping development of dermal complications, lowered the severity of the postvaccinal reaction and stimulated the cellular and humoral immune response. Ridostin, a high molecular interferon inductor, was highly efficient in cupping all the forms of the postvaccinal complications, including the neurological and cutaneous ones.

Investigation of the efficacy of ribavirin against the West Nile virus in standard cell cultures showed that in high concentrations it inhibited the virus reproduction (the inhibition coefficient of 100%). In the experiments on albino mice infected with the West Nile virus in a dose of 10 LD50 ribavirin was used in the form of injections in a dose of 20 mg/kg for 7 days in the scheme of urgent prophylaxis and proved to be highly efficient in protection of the animals from death (85-percent survival).

Ingavirin was shown to be efficient in inhibition of the influenza virus strains A/California/04/2009 and A/California/07/2009 (H1N1) in the MDCK cell culture. The coefficient of the cytopathic activity inhibition amounted to 50 and 60%, and the inhibition coefficients of the specific hemagglutinin formation were 50 and 50%, and 79,1 and 75% before and after the enrichment in chick embryos respectively.

Cytotoxicity of chemotherapeutics (Ribavirin, Remantadin and Ingavirin), interferon (Realdiron) and interferon inductors (Larifan, Ridostin, Arbidol and Cytarabin) was investigated with the use of persistent and diploid cell cultures. Ingavirin and Ribavirin from the group of the chemotherapeutics and Razifan and Ridostin from the group of the interferon inducrors showed the lowest toxicity. Light microscopy revealed no visible cytopathic changes in the investigation cell cultures exposed to maximum concentrations (> or =10(6) IU) of Realdiron. In vivo acute toxicity investigation demonstrated that in a concentration of 10(6) IU per animal weight Realdiron was not toxic for the albino mice and chinchilla rabbits. The maximum tolerance doses for the albino mice were the following: > or =3000 mg/kg of Ingavirin, 401.25 mg/kg of Arbidol, 170 mg/kg of Ribavirin, > or =100 mg/kg of Larifan and > or =100 mg/kg of Ridostin.

The experimental investigation of Ingavirin activity against influenza B virus showed that in concentrations 100 and 200 mcg/ml it was efficient in inhibition of the virus reproduction: the cytopathic effect was lowered by 75%, the level of the pathogen accumulation in the MDCK cell culture was decreased by more than 2.0 lg and the formation of the virus specific hemagglutinin was inhibited by more than 90%.

The comparative analysis of the efficacy of Ingavirin and etiotropic chemotherapeutics, such as Arbidol and Remantadin, against the influenza virus A (H3N2) performed with the use of susceptible permanent cell cultures showed that in the used concentrations Ingavirin was efficient in inhibition of the virus cytopathic activity, formation of the specific hemagglutinin and reproduction of the virus (by the accumulation).

The experimental investigation of the Ingavirin antiviral effect showed that in concentrations of 200 and 100 mcg/ml it totally protected the cells from the cytopathic action of the virus, when added before the inoculation of the HeLa cell culture. After a tenfold decrease of the infective dose (up to 0.001 CPD50/cell), the inhibition of the virus cytopathic effect by Ingavirin amounted to 100% in all the tested concentrations (including the low ones) added either before or after the culture contamination. Ingavirin was efficient in inhibition of the adenovirus type 5 reproduction in the HeLa cell culture.

The essence of studies was that the disease is simulated in 12-day albino mice subcutaneously infected with Hantaan virus, strain 76-118 in a dose of 10 LD50. As an efficiency index, the study of drugs uses major (death protection coefficient, mean animal lifetime) and auxiliary (virological: pathogen accumulation in the brain tissues of deceased animals) parameters, biochemical (the levels of creatinine, urea, alanine aminotransferase, aspartate aminotransferase, malonic dialdehyde), hematological (count of leukocytes, leukogram) ones; as well as interferon status (the levels of circulatory interferon, leukocytic production of alpha- and gamma-interferons). The procedure for simulating the disease caused by Hantaan virus on an experimental animal is used to choose effective drugs against the pathogen of hemorrhagic nephrosonephritis.

Experimental studies of arbidol and arbidol mesylate versus ribavirin suggest that insertion of these agents into the nutrient medium of the cultured cells GMK-AH-1 (D) after infection at concentrations of 50, 25, and 100 microg/ml, respectively, is effective in suppressing the reproduction of severe acute respiratory syndrome (SARS) virus. Arbidol and arbidol mesylate were shown to have a direct antiviral effect in early viral replication in the cultured cells. The promising antiviral agent is arbidol mesylate that is nearly 5 times as effective as arbidol in reducing the reproduction of SARS virus in the cultured cells. Insertion of arbidol, arbidol mesylate, and ribavirin into the nutrient medium 2 hours after infection of porcine embryonic renal cells caused a reduction in the accumulation of the pathogen by 2.5, 2.1, and 2.6 Ig, respectively.

Antiviral efficacy of Ingavirin was studied on albino mice infected intranasally by the grippe A virus (H3N2) vs. Tamiflu, Remantadin and Arbidol. Ingavirin used prophylactically in doses of 5 to 10 mg/kg was shown to be effective in protecting the animals from death and inhibiting the specific hemagglutinin formation and the virus reproduction in the lungs (by the accumulation).

Investigation of the therapeutic efficacy of Ingavirin (Valenta Farmacevtica, Russia) against influenza virus A (H3N2) vs. Tamiflu, Remantadin and Arbidol showed that in daily doses of 15 and 20 mg/kg (equal by the efficacy to the human doses of 90 and 120 mg) Ingavirin was effective in protection of the albino mice infected by the virus in a dose of 10 to 15 LD50. The protective efficacy was 38.3-39.2% and the increase of the average lifespan amounted to 4.2-4.4 days. The Ingavirin efficacy was comparable with that of Remantadine, markedly exceeded that of Arbidol and was lower than that of Tamiflu. Investigation of the Ingavirin influence in doses of 15 and 20 mg/kg on the dynamics and level of the influenza virus A/Aichi/2/68 reproduction in the lungs of the infected albino mice weighing 10-12 g revealed that during the whole observation period in the doses tested Ingavirin was effective in inhibition of the influenza virus reproduction. During the whole period of the observation (5 days) Ingavirin was effective in inhibiting the formation of the virus specific hemagglutinin in the target organ.

It is shown that primary screening of drugs against the pathogens of hemorrhagic fever with renal syndrome (HFV) may be performed, by using two approaches in estimating the suppression of plague formation and that of viral reproduction in the cultured cells. It is expedient to make a primary screening of interferon and its inductors to estimate the suppression of viral reproduction in the cultured Vero E6, PSEV, and CL-17 cells, the infection multiplicity should be hundredth parts of BOE/cell. Among the test agents, there are virazole and realdiron that are the most active drugs against Hantaan virus, 76-118 strain, which virually completely suppress the reproduction of the study causative agent, when used even at concentrations of 1-5 microg/ml and 100 U/ml, respectively.

Analysis of triazavirin efficacy with respect to influenza A virus (H5N1) in sensitive cell culture MDSK vs. effective antigrippe drugs, such as tamiflu, remantadin and arbidol showed that triazavirin in a wide range of the concentrations was efficient in inhibition of the virus cytopathic activity and formation of the specific hemagglutinin.

The antiviral effectiveness of the combined and single use of superlow-dose amixine and virasole on the course of experimental hemorrhagic fever with renal syndrome was studied in sucking albino mice parenterally infected with their virus Hantaan. The co-administration of virasole and amixine was shown to protect 52% of the infected animals from death, which is superior to the effect of their monotherapy. The combined use of the drugs substantially prolongs the survival of albino mice after their infection and the level of brain viral reproduction suppression ( delta = 3.21 g) in the experimental group as compared to the controls and to the mice given only one of the drugs.

Experimental research was undertaken to investigate the use of amixin in prevention, emergency prevention schemes and treatment of mice infected with West Nile fever (WNF) agent, strain Eg-101; the results are indicative of the drug efficiency both in its peroral and subcutaneous administrations. Amixin was shown to be most effective in the former case when administered, 10 mg/kg, in 96 hours before mice were infected as well as during the entire incubation period: lethality protection--46%. In the latter case, the drug was effective, when 3 administration schemes were in use, 10 mg/kg. The maximum degree of protection efficiency was registered with amixin administration according to the emergency prevention scheme: lethality protection--33%. The drug suppresses effectively the WNF virus reproduction in cerebral tissues.

Efficacy of drug therapy of Omsk hemorrhagic fever (OHF) was tested experimentally using cell culture and laboratory animals infected with the OHF virus strain Ondatra. Screening tests showed that high concentrations of Virazol or interferon inducers Larifan and Rifastin caused moderately pronounced suppression of virus reproduction in cell culture. Realdiron was found to be a high-efficacy preparation causing complete inhibition of virus reproduction in cell. Larifan demonstrated the highest antiviral efficacy against OHF virus in experiments with laboratory animals. This drug prevented the death of 65% infected mice and significantly decreased infection process severity in rabbits.

The experimental studies conducted on 2-week suckling mice infected with Hantaan virus, Strain 76-118) treated with oral and subcutaneous amoxine showed its prophylactic, therapeutical-and-prophylactic, and therapeutical efficiencies. Oral amoxine exhibited the highest efficiency when used in a dose of 10 mg/kg-1 96 hours before infection and throughout the incubation period. The protective efficiency was 61%. Subcutaneously, the agent was effective when three schemes for injection in a dose of 1 mg/kg-1. Its maximum effect was observed when amoxine was given by the therapeutical-and-prophylactic scheme. The death protection rate was 65%. The agent is effective in suppressing the reproduction of Hantaan virus in the brain tissue.

The comparative study of the specimens of the morphological elements of exanthema obtained from 8 children with the clinical diagnosis of secondary exogenic vaccinia, dried smallpox vaccine and the cultures of other orthopoxviruses (rabbit pox, monkey pox and buffalo pox viruses) was made. The isolation and identification of the causative agents from the specimens was carried out with the use of modern virological, electron microscopic and molecular methods. The study proved the fact that 8 children had orthopoxvirus infection with its causative agent identified as vaccinia virus.

The interferon-inducing and antiviral activities of high-molecular interferon inducers larifan and rifastin and of gene engineering human alpha 2-interferon were studied in monkeys infected with smallpox. These agents appreciably prolonged the life span of infected monkeys. For green monkeys the drug efficacies were as follows: larifan protected 50%, rifastin 86%, and realderon 50% (if used for treatment) and 80% (if used for urgent prophylaxis) of animals from death; for Papio hamadryas the efficacy of urgent prophylaxis was 60%. Interferon accumulated in the serum as early as during the first hours after injection of interferon inducers, the peak concentrations being observed after 3-6 h; for realderone the peak was observed after 9 h. The levels of interferon induction with larifan and rifastin were virtually the same.