Analysis of interaction mechanisms between main objects of tuberculosis-target therapy and corresponding selective inhibitors

  • D. O. Samofalova Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine
  • O. V. Rayevsky Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine
  • S. P. Ozheredov Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine
  • S. I. Spivak Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine
  • М. М. Stykhylias Institute of High Technologies of Taras Shevchenko National University of Kyiv
  • D. S. Ozheredov Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine
  • P. A. Karpov Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine


Aim. Search for new inhibitors of the mitotic apparatus of mycobacterium and a number of enzymatic targets. Methods. 3D models of key targets reconstruction and geometry optimization and analysis of biologically active conformations of inhibitors were performed according to a previously developed technique. Results. A revision of mycobacterial inhibitors, which exhibit antimicrobial action against representatives of the genus Mycobacterium, was carried out, which made it possible to create an appropriate reference library of compounds. The complete spatial structure of a number of the main targets of targeted therapy for tuberculosis was reconstructed and verified, and the features of their interaction with selective inhibitors were established. Chemogenomic profiling was performed, which made it possible to draw conclusions regarding the uniqueness of the studied sites and the potential toxicity of compounds related to these sites for humans. Conclusions. A well-developed search algorithm for known inhibitors of proteins with M. tuberculosis allows further study of the features of their interaction with the corresponding homologues of M. bovis and the development of new, more selective compounds using molecular dynamics and docking methods.

Keywords: tuberculosis, in silico, anti-tuberculosis drugs.


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