Pangenome Analysis of Mycobacterium tuberculosis Reveals Core-Drug Targets and Screening of Promising Lead Compounds for Drug Discovery

Antibiotics
Hamza Arshad DarAmjad Ali

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), is one of the leading causes of human deaths globally according to the WHO TB 2019 report. The continuous rise in multi- and extensive-drug resistance in M. tuberculosis broadens the challenges to control tuberculosis. The availability of a large number of completely sequenced genomes of M. tuberculosis has provided an opportunity to explore the pangenome of the species along with the pan-phylogeny and to identify potential novel drug targets leading to drug discovery. We attempt to calculate the pangenome of M. tuberculosis that comprises a total of 150 complete genomes and performed the phylo-genomic classification and analysis. Further, the conserved core genome (1251 proteins) is subjected to various sequential filters (non-human homology, essentiality, virulence, physicochemical parameters, and pathway analysis) resulted in identification of eight putative broad-spectrum drug targets. Upon molecular docking analyses of these targets with ligands available at the DrugBank database shortlisted a total of five promising ligands with projected inhibitory potential; namely, 2'deoxy-thymidine-5'-diphospho-alpha-d-glucose, uridine diphosphate glucose, 2'-deoxy-...Continue Reading

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Methods Mentioned

BETA
reverse transcription PCR

Software Mentioned

BPGA
Autodock
KEGG Automatic Annotation Server ( KAAS )
ProtParam
Autodock vina
VacSol
PyRx
TASSER
USEARCH
BLASTp

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