The recently discovered nonmevalonate pathway of isoprenoid biosynthesis Is a prospective target in screening of new antibiotics. Because of the absence of the pathway in the animal cells, the specific inhibitors of the pathway will be a new class of antibiotics against many pathogens (which cause e.g. malaria, tuberculosis, etc), combining high efficiency and low toxicity. Several derivatives of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (MEC) were synthesized. 4-Phospho-methyl-D-erythritol-1,2-cyclophosphate, benzyl ether and benzyliden derivative of MEC inhibited the¹⁴C-MEC incorporation into isoprenoids of chromoplasts from red pepper with IC₅₀ of 1.7-5 мМ. Some inhibition (about 10 %) was also observed with the use of dimethyl ether and isopropyliden derivative of MEC.

The data on antibacterial susceptibility and resistance of Vibrio cholerae eltor phenotypes with different sets of the susceptibility or resistance markers conditioning the outbreaks and sporadic cases of cholera in the Caucasus within 1970-1998 are presented. An increase of the number of the Vibrio cholerae phenotypes resistant to tetracycline and chloramphenicol usually used in the treatment of cholera was recorded in 1990-1994 vs. 1970-1989. The El Tor cholera vibrios stored on synthetic media lost some of their resistance markers, therefore the retrospective investigation of the antibioticograms was only of approximate prognostic value in the choice of the drugs for the etiotropic treatment of cholera in view of possible outbreak of the disease.

In antibiotic therapy it is necessary to use drugs active against the pathogen in its association with the host normal microflora. The aim of the study was to investigate modification of antibiotic resistance under conditions of the pathogen association with the representatives of the host normal microflora and to develop the microbiological criteria for determining effectiveness of antibacterials. Modification of microbial antibiotic resistance was investigated in 408 associations. Various changes in the antibiotic resistance of the strains were revealed: synergism, antagonism and indifference. On the basis of the results it was concluded that in the choice of the antibiotic active against Staphylococcus aureus and Streptococcus pyogenes the preference should be given to oxacillin, gentamicin and levomycetin, since the resistance of the pathogens to these antibiotics under the association conditions did not increase, which could contribute to their destruction, whereas the resistance of the normoflora increased or did not change, which was important for its retention in the biocenosis. The data on changeability of the antibiotic resistance of the microbial strains under the association conditions made it possible to develop microbiological criteria for determining effectiveness of antibiotics in the treatment of inflammatory diseases of microbial etiology (RF Patent No. 2231554).

Interaction of Glutoxime with P-glucoprotein (Pgp), a multiple drug resistance marker, as well as the Glutoxime impact on doxorubicin intracellular accumulation were investigated. It was shown that the Glutoxime effect on the Pgp expressing tumor cells resulted in a decrease of the cell specific fluorescence intensity, conditioned by binding of the monoclonal antibodies to the transport protein. That was evident of Glutoxime competition with the monoclonal antibodies for binding to Pgp and indicative of the modificator interaction with the transport protein. The effect was proved with the use of two cultures of human tumor cells of different histogenesis, i. e. the cells of Jurkat T-cellular leukemia and nonsmall cell lung cancer A549. Inhibition of the Pgp functional activity by Glutoxime was also demonstrateds. The authors suggested that it could be caused by direct competition of the modificator with the antitumor agent for binding to the precipitation sites on Pgp. Glutoxime could be considered as an inhibitor of multiple drug resistance associated with the Pgp function.

Despite obvious success in the vaccine development and chemotherapy of influenza, it remains a poorly controlled infection leading to emergence of new pandemic variants of the virus with high morbidity and mortality. We investigated the protective activity of Ingavirin® against the lethal influenza A(H1N1)2009 virus infection on albine mice. Oral use of Ingavirin® resulted in sharp decreasing of the mortality (index of protection up to 57%), slight decreasing of the infectious titer of the virus in the lungs (up to 40-fold), normalizing of the body weight dynamics and the lung tissue structure vs. the placebo-treated control. The degree of the bronchial epithelium damage was also strongly decreased. The results allow to consider Ingavirin® as an effective antiviral against the current pandemic influenza virus.

Ingavirin® was shown to be efficient in inhibition of the pandemic influenza virus strains A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009 (H1N1)v and A/Moscow/226/2009 (H1N1)v. as well as the influenza virus strain A/Aichi/2/68 (H3N2) in the lungs of the infected mice. After oral administration of Ingavirin® the titers of the influenza virus strains in the lung homogenates lowered.

Small-colony variants (SCVs), Isolated from a population of the parental strains of Staphylococcus aureus, S.haemolyticus and S.epidermidis lost a number of features typical of the species and genus and were characterized by delayed growth, altered colony morphology, lack of pigmentation and changed carbohydrate consumption. Some SCVs of S.aureus had no plasmocoagulase and lecithinase activities. The analysis of 14 SCVs showed that they were auxotrophic for hemin and menadione and resistant to aminoglycoside antibiotics. Such aberrant phenotypic characteristics complicated or made it impossible their identification by the common clinical laboratory methods. The tRNA intergenic spacer length polymorphism analysis was used to identify the atypical forms of the staphylococci.

Acute viral and bacterial intestinal infections in children provoke the Th2 immune response, resulting in development of severe and complicated forms of the disease and sustained by the disbiotic disturbances due to unnecessarily prolonged use of antibacterial drugs. Cycloferon, an early inductor of interferon-1 and -2, was shown to be safe and efficient in the complex therapy of the intestinal infections. It promoted generation of the Th2 immune response and decrease of the repeated isolation of the pathogen with normalization of the disease clinical signs. The host intestinal microflora was normalized and the level of the opportunistic organisms decreased.

The data on the efficacy of antivirals and their impact on the virologic and immunologic indices in HCV- and HBV-infected children are presented. The best therapeutic effect in the management of children with chronic virus hepatitis was provided by combined antiviral therapy of different action. In the treatment of babies the drugs of choice could be viferon or cycloferon, for the 2-year older children with chronic hepatitis B the combination of viferon + cycloferon should be recommended and for those with chronic hepatitis C the combination of interal + cycloferon could be used. The cycloferon combination with interferons-а makes it possible to generate the Th1 cellular immune response, to minimize the side effects of interferons and chemotherapeutics and to improve their tolerability. The complex therapy of patients with chronic hepatitis B and lambliasis, using cycloferon and macmiror, provided stable effect, less frequent relapses of lambliasis and minimum side effects of the specific therapy. The repeated isolation of lamblia within a 1-year observation period was recorded only in 16.6% of the children treated with cycloferon vs. the control (40.0%).