Impact of Target-Based Drug Design
in Anti-bacterial Drug Discovery
for the Treatment of Tuberculosis
Anju Choorakottayil Pushkaran, Raja Biswas and C. Gopi Mohan
Abstract Tuberculosis (TB) is an infectious disease caused by Mycobacterium
tuberculosis (Mtb) and is a major public health concern. According to the 2017
WHO report, global burden of TB infection was 10.4 million people causing the
mortality rate of *1.6 million. The rapid emergence of multidrug-resistant
(MDR) and extensively drug-resistant (XDR) TB is of major concern in anti-TB
drug discovery. There are different druggable targets and its pathways involved in
the virulence, which include Mtb cell wall, replication and transcription, regulatory,
protein synthesis, membrane transport, and energy production which need to be
explored for efficient killing of the bacteria. The ability of the tubercle bacilli to
remain within the host intracellular compartment is of other major concern in TB
therapy. Thus, to tackle the TB drug resistance, potent inhibitors with novel
mechanism of action of different Mtb druggable targets need to be discovered.
Three-dimensional structure of different Mtb target was solved for structure-based
drug design. The current chapter focuses on some of the key druggable targets in
Mtb and also the recent advances in target-based drug designing in the area of
anti-tubercular drug discovery.
Keywords Mycobacterium tuberculosis Á TB therapy Á Drug targets
Structural biology Á Chemoinformatics Á Drug resistance
Abbreviations
3D
Three-dimensional
ag85
Antigen 85
AMPK
5′adenosine monophosphate-activated protein kinase
AspS
Aspartyl tRNA synthetase
BCG
Bacille Calmette-Guérin
A. C. Pushkaran Á R. Biswas Á C. G. Mohan (&)
Center for Nanosciences and Molecular Medicine,
Amrita Institute of Medical Sciences and Research Centre,
Amrita Vishwa Vidyapeetham, Ponekkara, Kochi 682041, Kerala, India
e-mail: cgmohan@aims.amrita.edu
© Springer Nature Switzerland AG 2019
C. G. Mohan (ed.), Structural Bioinformatics: Applications in Preclinical Drug
Discovery Process, Challenges and Advances in Computational Chemistry
and Physics 27, https://doi.org/10.1007/978-3-030-05282-9_10
307
in Anti-bacterial Drug Discovery
for the Treatment of Tuberculosis
Anju Choorakottayil Pushkaran, Raja Biswas and C. Gopi Mohan
Abstract Tuberculosis (TB) is an infectious disease caused by Mycobacterium
tuberculosis (Mtb) and is a major public health concern. According to the 2017
WHO report, global burden of TB infection was 10.4 million people causing the
mortality rate of *1.6 million. The rapid emergence of multidrug-resistant
(MDR) and extensively drug-resistant (XDR) TB is of major concern in anti-TB
drug discovery. There are different druggable targets and its pathways involved in
the virulence, which include Mtb cell wall, replication and transcription, regulatory,
protein synthesis, membrane transport, and energy production which need to be
explored for efficient killing of the bacteria. The ability of the tubercle bacilli to
remain within the host intracellular compartment is of other major concern in TB
therapy. Thus, to tackle the TB drug resistance, potent inhibitors with novel
mechanism of action of different Mtb druggable targets need to be discovered.
Three-dimensional structure of different Mtb target was solved for structure-based
drug design. The current chapter focuses on some of the key druggable targets in
Mtb and also the recent advances in target-based drug designing in the area of
anti-tubercular drug discovery.
Keywords Mycobacterium tuberculosis Á TB therapy Á Drug targets
Structural biology Á Chemoinformatics Á Drug resistance
Abbreviations
3D
Three-dimensional
ag85
Antigen 85
AMPK
5′adenosine monophosphate-activated protein kinase
AspS
Aspartyl tRNA synthetase
BCG
Bacille Calmette-Guérin
A. C. Pushkaran Á R. Biswas Á C. G. Mohan (&)
Center for Nanosciences and Molecular Medicine,
Amrita Institute of Medical Sciences and Research Centre,
Amrita Vishwa Vidyapeetham, Ponekkara, Kochi 682041, Kerala, India
e-mail: cgmohan@aims.amrita.edu
© Springer Nature Switzerland AG 2019
C. G. Mohan (ed.), Structural Bioinformatics: Applications in Preclinical Drug
Discovery Process, Challenges and Advances in Computational Chemistry
and Physics 27, https://doi.org/10.1007/978-3-030-05282-9_10
307