[Streptomyces sp. 17, an organism producing oligomycin SC-iI (culture characteristics and antibiotic biological properties)].

Under the screening programme for organisms producing substances with hypolipidemic and antifungal activity Streptomyces sp. 17 was isolated. The taxonomic properties of the strain were investigated. Active compounds, i.e. oligomycin A and oligomycin SC-II were isolated from a complex biosynthetic product. Oligomycin A showed high antifungal activity whereas oligomycin SC-II had also moderate antibacterial activity.

[Physico-chemical properties and structure of oligomycin SC-II, produced by Streptomyces virginiae 17].

Under the screening programme for antibiotics with antifungal and immunosuppressive activities, Streptomyces virginiae 17 producing an oligomycin complex was isolated. Separation of the complex by HPLC showed that it contained two components at a ratio of 8:2. The physico-chemical characteristics of the components were investigated. The structure of oligomycin was assessed by 13C NMR and 1H NMR.

[Influence of natural complex compounds with hipolipidemic activity on expression of bacteria virulence factors].

Natural complex compounds with hipolipidemic activity, having considerable inhibitory effect on expression of bacteria virulence factors were isolated. Inhibitory properties of the compounds with respect to pyocyanine and protease formation, as well as their influence on the quorum sensing mechanism in Chromobacterium violacium were shown.

[Hyphomycetes as organisms producing cyclodepsipeptides].

The review deals with cyclodepsipeptides produced by hyphomycetes. The cyclodepsipeptide compounds are prospective new agents for the treatment of diseases of the infectious and pathophysiologic nature.

[Influence of natural hypolipidemic compounds on biofilm formation by Pseudomonas strains].

Natural compounds showing considerable inhibitory effect on formation of biofilms by P. aeruginosa were selected. Synergism of the compounds with gentamicin with respect to both the inhibition of the biofilm formation and the gentamicin antibacterial effect was stated.

[Complex of cyclosporins produced by Tolypocladium inflatum isolated from soil sample from Buriatiia].

A micromycete culture was isolated from a soil sample of Buryatiya and identified as Tolypocladium inflatum No. 2. The culture was shown to produce a complex of cyclosporins of unusual component structure: the content of cyclosporin A (55-60%) was the same as that in the substances produced by the majority of the described cultures, the content of cyclosporin B was much higher (about 40%) and the content of cyclosporin C was relatively low (about 3%). An appreciable content of cyclosporin (Leu4)Cs (3%) proved to be of interest.

[Organisms producing hypolipidemic compounds with antioxidant activity].

Complex compounds produced by fungal cultures of Lecanicilium and Beauveria with both high hypolipidemic and antioxydant activities were screened. Two fractions of the hypolipipidemic compounds with antioxidant activity of 95 and 75% in a dose of 25 mcg/ml were isolated.

[Tetravaccine--new fundamental approach to prevention of influenza pandemic].

According to opinion of WHO's experts, development and use of tetravaccine, which contains both interdemic and pandemic (H5N1) serotypes of influenza viruses, is one of the most promising approaches to control possible influenza pandemic. Results of recently obtained data from clinical trials allowed experts from WHO to make a conclusion that protective immunity against avian influenza virus can be achieved after 2-doses immunization, when the immune system will be primed to hemagglutinin after the 1st dose and sufficient protective immunity level will be formed after the 2nd dose. However, in case of real threat of pandemic, the time for immunization with 2 doses of the vaccine will be absent. In order to provide protection for population of Russia in a limited time frame it is reasonable to vaccinate them with H5 hemagglutinin beforehand. In that case, when real threat of pandemic will arise, not two but one injection with monovalent vaccine against avian influenza will be sufficient. This idea formed the basis for concept of development of tetravaccine. The essence of the concept is vaccination of population with tetravaccine, consisting of antigens of influenza virus serotypes H3N2, H1N1, B, and H5, before the influenza pandemic caused by H5N1 virus will begin. Such vaccination will induce immunologic memory to hemagglutinin of avian influenza virus serotype H5 and, when the real threat of the pandemic will occur, only single immunization with monovaccine against avian influenza instead of 2 doses will be required. In 2006 Scientific-Production Association "Microgen" conducted extended preclinical study of immunogenic and protective characteristics of candidate vaccines against avian influenza prepared from vaccine strains of H5N1 and H5N2 serotypes. It has been shown that candidate vaccines prepared from both strains have high protective ability against Russian epidemic isolate A/chicken/Kurgan/Russia/2/2005(H5N1). To this time Scientific-Production Association "Microgen" has produced monovalent bulk of H3N2, H1N1, and B serotypes, which are included in interdemic influenza vaccines, as well as monovalent bulk of H5N1 and H5N2 serotypes. This intermediate products are ready to be produced into tetravaccine for conducting extended preclinical studies of its safety, reactogenicity, immunogenicity, and protective properties. If results of such studies will be positive then it is possible to begin clinical trials of the tetravaccine in 2007 and to discuss the questions about its dosage, methods of challenge and schedule.

[Comparative clinical trial of vaccines against avian influenza].

Scientic-production association "Microgen" has finished 1st phase of clinical trials of candidate vaccines against avian influenza in order to assess their reactogenicity, safety, and immunogenicity. Two vaccines constructed from NIBRG-14 vaccine strain [A/Vietnam/1 194/2004 (H5N1)], obtained from World Health Organization, were studied: "OrniFlu" (inactivated subunit influenza vaccine adsorbed on aluminium hydroxide) and inactivated polymer-subunit influenza vaccine with polyoxydonium (IPSIV). Clinical trial of the vaccines with different quantity of antigen (15, 30, and 45 mcg of H5N1 virus hemagglutinin) was carried out in Influenza Research Institute (St. Petersburg) and in Mechnikov Research Institute of Vaccines and Sera (Moscow). Analysis of results allowed to conclude that both vaccines were safe, well tolerated and characterized by low reactogenicity. Two-doses vaccination schedule was needed to meet required seroconversion and seroprotection rates (> or =1:40 in > or =70% of vaccinated volunteers). "Orni-Flu" vaccine containing 15 mcg of hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) in one dose as well as IPSIV containing 45 mcg of hemagglutinin and 0.75 mg of polyoxydonium in one dose were most immunogenic after 2 doses - seroprotection rates in microneutralization assay were 72.2% and 77.0% respectively. Marked influence of aluminium hydroxide content on immunogenicity of the "OrniFlu" vaccine was confirmed in the study. Optimal quantity of adjuvant was 0.5 mg per dose. According to basic concept of vaccine development, preference is given to vaccine that under minimal quantity of antigen induces sufficient specific immune response and is safe in volunteers. "OrniFlu" vaccine containing 15 mcg of H5N1 virus hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) corresponded to these requirements that allowed researchers to recommend it for clinical trials of 2nd phase.

[Antimicrobial activity of natural hypolipidemic compounds].

Antibiotic activity of complex agents of actinomycete and fungal origin was studied in the programme of screening organisms producing substances with hypolipidemic activity. The majority of the agents were shown to be active against Aspergillus niger 137a and Candida albicans ATCC 885-653. Some of the agents were active against bacteria, including acid-fast ones.

[Lovastatin effect on ergosterol production and growth of Tolypocladium inflatum 106]. / Vliianie lovastatina na rost i obrazovanie érgosterola kul'turoi Tolypocladium inflatum 106.

The effect of lovastatin on Tolypocladium inflatum 106 was studied. The strain was shown to be highly sensitive to lovastatin when its MIC was determined by the agar diffusion method and under submerged conditions that was considered possible to use the strain as a test culture in screening of new natural compounds with hypolipidemic action and to study its specificity. It was demonstrated that the effect of lovastatin on ergosterol synthesis in T. inflatum 106 was of specific dose-dependent polymodal nature.

[Effect of novel natural hypolipidemic compounds on human immunodeficiency virus]. / Vliianie novykh prirodnykh gipolipidemicheskikh soedinenii na virus immunodefitsita cheloveka.

Target screening among microbial products resulted in isolation of hypolipidemic compounds tested for activity against HIV in culture of transferable lymphoblastoid cells MT-4. The majority of the compounds showed antiviral activity. The highest antiviral effect was observed when before exposure to the virus the cells were preincubated for 1 hour in the presence of the isolated compounds. The compounds showed no effect when added to the cell culture preliminarily infected by HIV.

[Screening of natural compounds with hypolipidemic activity]. / Skrining prirodnykh soedinenii s gipolipidemicheskoi aktivnost'iu.

In the screening programme for natural hypolipidemic compounds 702 strains of soil microorganisms were tested and 25 of them were selected because of their ability to produce compounds inhibiting sterol synthesis in Hep G2 hepatoma cells. The compounds were estimated in the microbiological model with Tolypocladium inflatum 106 as the test microbe. The 2nd stage of the screening resulted in isolation of 13 strains producing compounds with high hypolipidemic activity, analogous to or higher than the activity of lovastatin in the experimental models.

[Estimation of the efficacy of screened natural hypolipidemic compounds in a model of rabbit hypercholesterolemia]. / Otsenka éffektivnosti otobrannykh prirodnykh gipolipidemicheskikh veshchestv na modeli giperkholesterinemii u krolikov.

Thirteen strains producing hydrophobic compounds with high hypolipidemic activity were screened among 657 tested strains of fungi, actinomycetes and bacteria with the use of 2 models. The further aim of the study was to estimate the efficacy of the compounds with respect to their ability to inhibit cholesterol synthesis in vivo. For that purpose a model of hyperlipidemia in rabbits was used. The model provided screening of 9 new compounds that showed satisfactory hypolipidemic effect evident from a significant decrease of the lipid levels in the rabbit serum. The study of the serum lipid profile revealed that the inhibitory effect of compounds No. 16 and No. 281 was similar to that of lovastatin whereas the serum level of general cholesterol remained decreased for a longer period. Compound No. 25 was of interest because of its possible use in low doses and significant effect on the serum triglyceride fraction.

[Streptomyces griseolus # 182--a novel organism producing oligomycin antibiotics. Taxonomy, fermentation, and isolation]. / Novyi produtsent antibiotikov oligomitsinovoi struktury Streptomyces griseolus No 182. Taksonomiia, fermentatsiia i vydelenie.

Target screening of natural immunosuppressors resulted in isolation of a strain of Streptomyces griseolus (No. 182) producing a complex of antifungal antibiotics. The strain proved to be an aerobe with the growth temperature of 26 to 28 degrees C. Morphological features and physiological properties of the strain were studied. Scanning electron microscopy revealed smooth, oval spores 1.10-1.25 mu in size. The findings showed that the strain belonged to Streptomyces griseolus. Unlike the previously described organisms producing the oligomycin complex the new strain formed straight or twisted sporophores and did not produce melanoid pigment or soluble pigment when grown on the Gauze mineral agar medium No. 1. The procedures for biosynthesis and chemical recovery of the antibiotic complex from the mycelium are described. The complex was shown to include 3 components at a ratio of 80:15:5 identified as oligomycins A, B and C respectively. The oligomycin complex was highly active against Aspergillus niger 137, Tolypocladium inflatum, Fusarium ocsisporum, Curvularia lunata 645 and Trichoderma alba F-32 (MIC 0.1-1.0 mcg/ml). The activity against yeast and bacterial cultures was observed only when the doses were higher than 100 mcg/ml.