Rediscovering and repurposing natural microbial macromolecules through computational approaches

Abdella, Mohamed; Abdella, Bahaa; Lahiri, Chandrajit

doi:10.1016/b978-0-12-820084-1.00016-8

Cited by 5 publications

(4 citation statements)

References 130 publications

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“…Over the years, the commendable development in the field of virtual screening has enabled time- and cost-efficient drug discovery along with repurposing 35 . Herein, we have carried out a scaffolded approach to antimicrobial drug discovery from a yellow variety of Malaysian N. lappaceum L. fruit epicarp crude extracts.…”

Section: Discussionmentioning

confidence: 99%

A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L.

Ali

Tan

Zahoor

et al. 2021

Sci Rep

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The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC–MS and GC–MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.

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Section: Discussionmentioning

confidence: 99%

A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L.

Ali

Tan

Zahoor

et al. 2021

Sci Rep

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“…Over time, creditable progress in the field of virtual screening has permitted time- and cost-efficient drug discovery with repurposing ( Abdella et al, 2020 ). Thus, we have considered a similar approach to antibacterial drug discovery from the CEF of Malaysian red seaweed, G. edulis .…”

Section: Discussionmentioning

confidence: 99%

Metabolite Profiling of Malaysian Gracilaria edulis Reveals Eplerenone as Novel Antibacterial Compound for Drug Repurposing Against MDR Bacteria

et al. 2021

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With a continuous threat of antimicrobial resistance on human health worldwide, efforts for new alternatives are ongoing for the management of bacterial infectious diseases. Natural products of land and sea, being conceived to be having fewer side effects, pose themselves as a welcome relief. In this respect, we have taken a scaffolded approach to unearthing the almost unexplored chemical constituents of Malaysian red seaweed, Gracilaria edulis. Essentially, a preliminary evaluation of the ethyl acetate and acetone solvent extracts, among a series of six such, revealed potential antibacterial activity against six MDR species namely, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, and Bacillus subtilis. Detailed analyses of the inlying chemical constituents, through LC-MS and GC-MS chromatographic separation, revealed a library of metabolic compounds. These were led for further virtual screening against selected key role playing proteins in the virulence of the aforesaid bacteria. To this end, detailed predictive pharmacological analyses added up to reinforce Eplerenone as a natural alternative from the plethora of plausible bioactives. Our work adds the ongoing effort to re-discover and repurpose biochemical compounds to combat the antimicrobial resistance offered by the Gram-positive and the -negative bacterial species.

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“…Besides the above, bioinformatics approaches downstream of drug target identification often include virtual screening via molecular docking and MD simulation, and hence, experimentally crystallised protein 3D structures have become a godsend in recent research (29,30,145). In this regard, in a study, researchers have crystallised the 3D structures of 29 essential proteins in A. baumannii and deposited them in Protein Data Bank (PDB), fifteen (15) of which were recommended to be druggable, based on active site features and sequence homology (146).…”

Section: In-silico Methods In Mining Novel Drug Targetsmentioning

confidence: 99%

Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years

Tan

Lahiri

2022

Front. Immunol.

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In parallel to the uncontrolled use of antibiotics, the emergence of multidrug-resistant bacteria, like Acinetobacter baumannii, has posed a severe threat. A. baumannii predominates in the nosocomial setting due to its ability to persist in hospitals and survive antibiotic treatment, thereby eventually leading to an increasing prevalence and mortality due to its infection. With the increasing spectra of drug resistance and the incessant collapse of newly discovered antibiotics, new therapeutic countermeasures have been in high demand. Hence, recent research has shown favouritism towards the long-term solution of designing vaccines. Therefore, being a realistic alternative strategy to combat this pathogen, anti-A. Baumannii vaccines research has continued unearthing various antigens with variable results over the last decade. Again, other approaches, including pan-genomics, subtractive proteomics, and reverse vaccination strategies, have shown promise for identifying promiscuous core vaccine candidates that resulted in chimeric vaccine constructs. In addition, the integration of basic knowledge of the pathobiology of this drug-resistant bacteria has also facilitated the development of effective multiantigen vaccines. As opposed to the conventional trial-and-error approach, incorporating the in silico methods in recent studies, particularly network analysis, has manifested a great promise in unearthing novel vaccine candidates from the A. baumannii proteome. Some studies have used multiple A. baumannii data sources to build the co-functional networks and analyze them by k-shell decomposition. Additionally, Whole Genomic Protein Interactome (GPIN) analysis has utilized a rational approach for identifying essential proteins and presenting them as vaccines effective enough to combat the deadly pathogenic threats posed by A. baumannii. Others have identified multiple immune nodes using network-based centrality measurements for synergistic antigen combinations for different vaccination strategies. Protein-protein interactions have also been inferenced utilizing structural approaches, such as molecular docking and molecular dynamics simulation. Similar workflows and technologies were employed to unveil novel A. baumannii drug targets, with a similar trend in the increasing influx of in silico techniques. This review integrates the latest knowledge on the development of A. baumannii vaccines while highlighting the in silico methods as the future of such exploratory research. In parallel, we also briefly summarize recent advancements in A. baumannii drug target research.

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Rediscovering and repurposing natural microbial macromolecules through computational approaches

Cited by 5 publications

References 130 publications

A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L.

A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L.

Metabolite Profiling of Malaysian Gracilaria edulis Reveals Eplerenone as Novel Antibacterial Compound for Drug Repurposing Against MDR Bacteria

Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years

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