Title:New and Old Hot Drug Targets in Tuberculosis
Volume: 23
Issue: 33
Author(s): Laurent Roberto Chiarelli, Giorgia Mori, Marta Esposito, Beatrice Silvia Orena and Maria Rosalia Pasca
Affiliation:
Keywords:
Tuberculosis, antitubercular drugs, repurposed targets, promiscuous targets, phenotypic screening, drug
design.
Abstract: Tuberculosis is an infectious disease caused by the bacillus Mycobacterium tuberculosis.
The World Health Organization publishes global tuberculosis reports annually in
order to provide the latest information in the surveillance of drug resistance. Given the
alarming rise of resistance to antitubercular drugs worldwide, finding new cellular targets
and developing new analogues or new compounds with greater potency against already
known targets are both important aspects in fighting drug-sensitive and drug-resistant M.
tuberculosis strains. In this context, the introduction of the phenotypic screens as an efficient
tool for the identification of active compounds for tuberculosis drug discovery has improved
the possibility to find new effective targets.
With this review we describe the state of art of the currently well validated antitubercular
drug targets as well as the advances in discovery of new ones. The main targets will be discussed
starting from the oldest such as the enoyl reductase InhA which is constantly repurposed
with new inhibitors, through the well assessed targets like the gyrase, the ATP synthetase
or the RNA polymerase, up to the hot promiscuous targets decaprenylphosphoryl-Dribose
oxidase DprE1 and the mycolic acid transporter MmpL3, or the newly validated and
promising targets like the CTP synthetase.
