Protein Integrated Network Analysis to Reveal Potential Drug Targets Against Extended Drug-Resistant Mycobacterium tuberculosis XDR1219

Zahra, Noor-ul-Ain; Jamil, Faiza; Uddin, Reaz

doi:10.1007/s12033-021-00377-w

Cited by 6 publications

(1 citation statement)

References 75 publications

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“…First, we generated a protein–protein interaction network from the high confidence interaction data [ 24 ]. The network embedding is only possible with the network’s largest connected component (LCC).…”

Section: Resultsmentioning

confidence: 99%

Selection of Multi-Drug Targets against Drug-Resistant Mycobacterium tuberculosis XDR1219 Using the Hyperbolic Mapping of the Protein Interaction Network

Zahra,

Vagiona,

Uddin

et al. 2023

IJMS

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Tuberculosis remains the leading cause of death from a single pathogen. On the other hand, antimicrobial resistance (AMR) makes it increasingly difficult to deal with this disease. We present the hyperbolic embedding of the Mycobacterium tuberculosis protein interaction network (mtbPIN) of resistant strain (MTB XDR1219) to determine the biological relevance of its latent geometry. In this hypermap, proteins with similar interacting partners occupy close positions. An analysis of the hypermap of available drug targets (DTs) and their direct and intermediate interactors was used to identify potentially useful drug combinations and drug targets. We identify rpsA and rpsL as close DTs targeted by different drugs (pyrazinamide and aminoglycosides, respectively) and propose that the combination of these drugs could have a synergistic effect. We also used the hypermap to explain the effects of drugs that affect multiple DTs, for example, forcing the bacteria to deal with multiple stresses like ethambutol, which affects the synthesis of both arabinogalactan and lipoarabinomannan. Our strategy uncovers novel potential DTs, such as dprE1 and dnaK proteins, which interact with two close DT pairs: arabinosyltransferases (embC and embB), Ser/Thr protein kinase (pknB) and RNA polymerase (rpoB), respectively. Our approach provides mechanistic explanations for existing drugs and suggests new DTs. This strategy can also be applied to the study of other resistant strains.

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Section: Resultsmentioning

confidence: 99%

Selection of Multi-Drug Targets against Drug-Resistant Mycobacterium tuberculosis XDR1219 Using the Hyperbolic Mapping of the Protein Interaction Network

Zahra,

Vagiona,

Uddin

et al. 2023

IJMS

Self Cite

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Bridging drug discovery through hierarchical subtractive genomics against asd, trpG, and secY of pneumonia causing MDR Staphylococcus aureus

Wisal,

Saeed,

Aurongzeb

et al. 2024

Mol Genet Genomics

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Staphylococcus aureus (S. aureus) is an opportunistic gram-positive, non-motile, and non-sporulating bacteria that induce pneumonia, a provocative lung infection affecting mainly the terminal bronchioles and the small air sacs known as alveoli. Recently, S. aureus has developed resistance to the available antibiotics consortium as per WHO reports, thereby, novel remedial targets and strong medications to forestall and cure this illness are desperately needed.Here, using pangenomics, a total of 1,387 core proteins were identi ed. Subtractive proteome analysis is utilized to further identify 12 proteins that are vital for bacteria. One membrane protein (secY) and two cytoplasmic proteins (asd and trpG) were chosen as possible therapeutic targets with respect to minimum % host identity, essentiality, and other cutoff values such as high resistance in MDR S. aureus. The amino acid sequence of selected targets was modeled and then docked against drug-like chemical libraries. The top-ranked compounds i.e., ZINC82049692, ZINC85492658 and 3a of Isosteviol derivative for Aspartatesemialdehyde dehydrogenase (asd); ZINC38222743, ZINC70455378, and 5m Isosteviol derivative for Anthranilate synthase component II (trpG); and nally, ZINC72292296, ZINC85632684, and 7m Isosteviol derivative for Protein translocase subunit SecY (secY), were further subjected to molecular dynamics studies for thermodynamic stability and validation. In this study, we discovered new therapeutic targets in S. aureus, some of which have previously been reported in other pathogenic microorganisms. Owing to further experimental validation, We anticipate that our method and results will make major contributions in the discovery of novel drugs and their targets in S. aureus-caused pneumonia.

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The Gene Network Correlation Analysis of Obesity to Type 1 Diabetes and Cardiovascular Disorders: An Interactome-Based Bioinformatics Approach

D’Souza,

Khan,

Jalal

et al. 2023

Mol Biotechnol

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Protein Integrated Network Analysis to Reveal Potential Drug Targets Against Extended Drug-Resistant Mycobacterium tuberculosis XDR1219

Cited by 6 publications

References 75 publications

Selection of Multi-Drug Targets against Drug-Resistant Mycobacterium tuberculosis XDR1219 Using the Hyperbolic Mapping of the Protein Interaction Network

Selection of Multi-Drug Targets against Drug-Resistant Mycobacterium tuberculosis XDR1219 Using the Hyperbolic Mapping of the Protein Interaction Network

Bridging drug discovery through hierarchical subtractive genomics against asd, trpG, and secY of pneumonia causing MDR Staphylococcus aureus

The Gene Network Correlation Analysis of Obesity to Type 1 Diabetes and Cardiovascular Disorders: An Interactome-Based Bioinformatics Approach

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