Identification of potential drug targets by subtractive genome analysis of Bacillus anthracis A0248: An in silico approach

Rahman, Md. Anisur; Noore, Md. Sanaullah; Hasan, Md. Anayet; Ullah, Md. Rakib; Rahman, Md. Hafijur; Hossain, M. Amzad; Ali, Yeasmeen; Islam, Saiful

doi:10.1016/j.compbiolchem.2014.09.005

Cited by 32 publications

(15 citation statements)

References 52 publications

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“…In this server users can exploit 10–90% sequence identity in the “sequence identity cut-off” box depending on their requirement (Huang et al, 2010). It has been widely accepted to set 60% sequence identity as cut-off to maintain a rigid criteria to remove duplicate proteins (Dutta et al, 2006; Barh and Kumar, 2009; Rahman et al, 2014; Mondal et al, 2015; Hasan et al, 2016). Therefore, we have used CDHIT server (http://weizhong-lab.ucsd.edu/cdhit_suite/cgi-bin/index.cgi?cmd=cd-hit) in which 0.6 (60%) was manually set in “sequence identity cut-off” box for the stringent selection of duplicate proteins.…”

Section: Methodsmentioning

confidence: 99%

Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration

Hossain

Khan²,

Hashem³

et al. 2016

Front. Microbiol.

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Background: Shigella flexneri is a gram negative bacteria that causes the infectious disease “shigellosis.” S. flexneri is responsible for developing diarrhea, fever, and stomach cramps in human. Antibiotics are mostly given to patients infected with shigella. Resistance to antibiotics can hinder its treatment significantly. Upon identification of essential therapeutic targets, vaccine and drug could be effective therapy for the treatment of shigellosis.Methods: The study was designed for the identification and qualitative characterization for potential drug targets from S. flexneri by using the subtractive proteome analysis. A set of computational tools were used to identify essential proteins those are required for the survival of S. flexneri. Total proteome (13,503 proteins) of S. flexneri was retrieved from NCBI and further analyzed by subtractive channel analysis. After identification of the metabolic proteins we have also performed its qualitative characterization to pave the way for the identification of promising drug targets.Results: Subtractive analysis revealed that a list of 53 targets of S. flexneri were human non-homologous essential metabolic proteins that might be used for potential drug targets. We have also found that 11 drug targets are involved in unique pathway. Most of these proteins are cytoplasmic, can be used as broad spectrum drug targets, can interact with other proteins and show the druggable properties. The functionality and drug binding site analysis suggest a promising effective way to design the new drugs against S. flexneri.Conclusion: Among the 53 therapeutic targets identified through this study, 13 were found highly potential as drug targets based on their physicochemical properties whilst only one was found as vaccine target against S. flexneri. The outcome might also be used as module as well as circuit design in systems biology.

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Section: Methodsmentioning

confidence: 99%

Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration

Hossain

Khan²,

Hashem³

et al. 2016

Front. Microbiol.

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“…The subtractive genomics approach is very efficient and has greatly accelerated the identification of relevant drug targets against many pathogens such as M. tuberculosis and Bacillus anthracis (Hosen et al, 2014;Rahman et al, 2014). Large-scale genomic projects such as the 1000 Genome and Encode are a rich source of background information and provide a deeper understanding of the genomes in relation to diseases.…”

Section: Discussionmentioning

confidence: 99%

Novel Drug Targets for Food-Borne PathogenCampylobacter jejuni: An Integrated Subtractive Genomics and Comparative Metabolic Pathway Study

Mehla

Ramana

2015

OMICS: A Journal of Integrative Biology

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Campylobacters are a major global health burden and a cause of food-borne diarrheal illness and economic loss worldwide. In developing countries, Campylobacter infections are frequent in children under age two and may be associated with mortality. In developed countries, they are a common cause of bacterial diarrhea in early adulthood. In the United States, antibiotic resistance against Campylobacter is notably increased from 13% in 1997 to nearly 25% in 2011. Novel drug targets are urgently needed but remain a daunting task to accomplish. We suggest that omics-guided drug discovery is timely and worth considering in this context. The present study employed an integrated subtractive genomics and comparative metabolic pathway analysis approach. We identified 16 unique pathways from Campylobacter when compared against H. sapiens with 326 non-redundant proteins; 115 of these were found to be essential in the Database of Essential Genes. Sixty-six proteins among these were non-homologous to the human proteome. Six membrane proteins, of which four are transporters, have been proposed as potential vaccine candidates. Screening of 66 essential non-homologous proteins against DrugBank resulted in identification of 34 proteins with drug-ability potential, many of which play critical roles in bacterial growth and survival. Out of these, eight proteins had approved drug targets available in DrugBank, the majority serving crucial roles in cell wall synthesis and energy metabolism and therefore having the potential to be utilized as drug targets. We conclude by underscoring that screening against these proteins with inhibitors may aid in future discovery of novel therapeutics against campylobacteriosis in ways that will be pathogen specific, and thus have minimal toxic effect on host. Omics-guided drug discovery and bioinformatics analyses offer the broad potential for veritable advances in global health relevant novel therapeutics.

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“…Nowadays, for the development of potential drug and vaccine targets against various infective pathogens, the most effective choice is computational based techniques (Amineni et al 2010;Barh and Kumar 2009;Damte et al 2013;Hasan et al 2016;Oany et al 2014bOany et al , 2017. The essential protein set for pathogen survival, however not in the host, can be identified by using subtractive and comparative genomics approach combined with metabolic pathway (Rahman et al 2014). Identification of non-homologous essential genes for pathogens by subtraction from both host and pathogen metabolic pathway assures no interaction of drugs with host targets.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential drug targets and inhibitor of the pathogenic bacteria Shigella flexneri 2a through the subtractive genomic approach

Oany¹,

Mia²,

Pervin³

et al. 2018

In Silico Pharmacol.

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Shigella flexneri 2a is one of the most pathogenic bacteria among the Shigella spp., which is responsible for dysentery and causes masses of deaths throughout the world per year. A proper identification of the potential drug targets and inhibitors is crucial for the treatment of the shigellosis due to their emerging multidrug resistance (MDR) patterns. In this study, a systematic subtractive approach was implemented for the identification of novel therapeutic targets of S. flexneri 2a (301) through genome-wide metabolic pathway analysis of the essential genes and proteins. Ligand-based virtual screening and ADMET analyses were also made for the identification of potential inhibitors as well. Initially, we found 70 essential unique proteins as novel targets. After subsequent prioritization, finally we got six unique targets as the potential therapeutic targets and their three-dimensional models were built thereafter. Aspartate-β-semialdehyde dehydrogenase (ASD), was the most potent target among them and used for docking analysis through ligand-based virtual screening. The compound 3 (PubChem CID: 11319750) suited well as the best inhibitor of the ASD through ADMET and enzyme inhibition capacity analysis. To end, we hope that our proposed therapeutic targets and its inhibitors might give some breakthrough to treat shigellosis efficiently in in vitro.

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Identification of potential drug targets by subtractive genome analysis of Bacillus anthracis A0248: An in silico approach

Cited by 32 publications

References 52 publications

Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration

Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration

Novel Drug Targets for Food-Borne PathogenCampylobacter jejuni: An Integrated Subtractive Genomics and Comparative Metabolic Pathway Study

Identification of potential drug targets and inhibitor of the pathogenic bacteria Shigella flexneri 2a through the subtractive genomic approach

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