A consequence of drug targeting of aminoacyl-tRNA synthetases in Mycobacteriumtuberculosis

Chem Biol Drug Des. 2021 Sep;98(3):421-434. doi: 10.1111/cbdd.13865. Epub 2021 Jul 3.

Abstract

Drug-resistant Mycobacterium tuberculosis poses a great threat to public health and remains one of the red-flag tagged infectious diseases, with the tendency of comorbidity with other disease conditions such as HIV/AIDS. This perhaps is responsible for redoubling of effort in tuberculosis research and continuous change in patient management to optimize the drug therapy. Aminoacyl-tRNA synthetases are essential enzymes in M. tuberculosis that catalyse the transfer of a particular amino acid to its corresponding specific tRNA to form an aminoacyl-tRNA. These enzymes are believed to be novel antibacterial, antifungal and antiparasitic drug targets because of their role in the process of protein translation. Therefore, their existence as a compliment of M. tuberculosis has attracted a lot of research interest with the aim of curbing the scourge and provide the most effective drug in the treatment of tuberculosis. This leads to the discovery of a pool of aminoacyl-tRNA synthetases with their essential inhibitors. This review seeks to articulate the current advances in the development of new TB drugs exhibiting novelty in their mode of action with specific emphasis on aminoacyl-tRNA synthetases as drug targets.

Keywords: Mycobacterium tuberculosis; aminoacyl-tRNA synthetase; drug-resistance and drug target.

Publication types

  • Review

MeSH terms

  • Amino Acyl-tRNA Synthetases / antagonists & inhibitors*
  • Amino Acyl-tRNA Synthetases / metabolism
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / metabolism
  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Drug Resistance, Bacterial / drug effects
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Molecular Docking Simulation
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology*

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Amino Acyl-tRNA Synthetases