Page 72 - Annual report 2021-22

Annual Report 2021-22 |

S. Ramachandran

55

Emergence of multi drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium
tuberculosis poses a serious threat to TB control as the available treatment options are less effective
in these cases. Therefore, new strategies are required for identification of new drugs and drug targets.
Their work is aimed to find one such small molecule inhibitor against Mtb-DapA and to make a
comprehensive repository of multifaceted antimicrobial therapeutic strategies.
Identification of small molecule inhibitors against Mtb-DapA:

This study uses a comprehensive approach to screen both substrate (pyruvate) and product analogues
of DapA. Small molecule inhibitors are shortlisted and validated using in silico and in vitro approaches.
For in vitro validation, coupled enzymatic assay and fluorescent based thermal shift assay was
performed. Although the initial approach did not show a potent inhibition, a change of design based
on the idea that the substrate and product analogue could target Mtb-DapA and Mtb-DapB
respectively produced strong inhibition. Various concentrations of substrate (alpha-Ketopimelic acid,
Tartronic acid) and product analogues (2,6-Pyridine dicarboxylic acid) were used. It was observed that,
the percentage inhibition increased to nearly 100% when coupled assay was performed by
combination of 20µM alpha-Ketopimelic acid with 200µM 2,6-Pyridine dicarboxylic acid and 50µM
Tartronic acid with 200µM 2,6-Pyridine dicarboxylic acid.

Development of KOMBAT- A Knowledgebase Of Microbe Battling Agents for Therapeutics;

Kombat (http://kombat.igib.res.in/) consists of data collected through systematic and thorough
methods of literature mining. Currently, the knowledgebase includes the following six data categories.

● Bacteriophage therapy: 21 manually curated phage therapy strategies.
● Antimicrobial peptide: 68 antibacterial peptides, 35 antifungal peptides, 19 antiviral peptides
and 5 antiparasitic peptides having therapeutic potential are reported. Novel antimicrobial
peptides and combinatorial therapeutic strategies of AMPs with photosensitizer or existing
antibiotics are reported here.
● Phytochemicals and natural products: 140 manually curated phytochemicals and extracts
from natural products. It comprises 86 antibacterial, 29 antifungal, 17 antiviral and 8
antiparasitic therapeutic strategies.
● Nanocomposites: 57 manually curated therapeutic strategies developed using
nanostructures. Among them 46 are antibacterial, 8 are antifungal and 3 are antiviral.
● Photodynamic therapy: 48 strategies for photodynamic inactivation of microbial pathogens
have been included. Among them 39 are for bacterial pathogens and 9 are for fungal
pathogens.
● Chemical compounds: 852 newly discovered compounds with therapeutic potential against
diverse microbial pathogens. The list comprises 340 antibacterial, 392 antiviral, 110 antifungal
and 10 antiparasitic compounds.

Ramachandran also participated in collaborative projects to apply his skills to other infectious diseases
like investigation of mechanisms of emerging drug resistance in trichophyton sp., the major causative