[The choice of the targets and the search for their inhibitors by means of computer simulation for the development of innovative preparations to treat of chronic bacterial infections].

Persistence is a form of interaction of pathogenic bacteria with a host aimed to promote their long-term survivalby means of inactivation of the host's protective systems via modulation of intracellular signal pathways. Persistent forms of a pathogen are refractory to traditional antibiotic therapy and cause chronic infectious diseases. Directed search for protein targets and new antibacterial drugs using computer simulation and experimental testing for the development of innovative preparations to treat chronic bacterial infections appears to have good prospects as a method for the management of persistent infections. A stepwise strategy for realization of such approach is exemplified by the search of preparations against chlamydial infection.

[Target-directed search of anti-virulence drugs].

Modern medicine now encounters with problem of the absence of effective antibacterial drugs, which are able to render therapeutic effect on chronic form of infectious process. Thus, the actual objective is to develop essentially new generation of drugs, on the basis of which should lie identification of new bacterial targets playing key role in process of chronization of infection as well as selection of new physiologically active substances, which are able to render highly specific inhibitory effect on selected target. Solving of this objective is possible during realization of new approaches for search and design of new drugs and, first of all, during usage of bioinformatics methods, which enable to identify new biotargets, select most effective chemical compounds-inhibitors and optimize their pharmacological and pharmacokinetic properties. The most promising bacterial target is secretion systems of pathogenic microorganisms participating in realization of their virulent characteristics and playing major role in transition of infectious process in chronic phase. We performed synthesis of and screening for 80 compounds, which allowed to select a range of inhibitors rendering specific target-directed effect on type 3 secretion system of Chlamydia. Obtained data allow to further assess of biological and therapeutic activity of these compounds on developed models of infectious process in vivo.