scholarly journals Metabolic pathway analysis in trypanosomes and malaria parasites

2002 ◽  
Vol 357 (1417) ◽  
pp. 101-107 ◽  
Author(s):  
Alan H. Fairlamb
Keyword(s):  
Drug Target ◽  
Drug Targets ◽  
Target Identification ◽  
Potential Drug ◽  
Metabolic Pathway Analysis ◽  
Entire Genome ◽  
Microbial Responses ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

Identification of novel drug targets is required for the development of new classes of drugs to overcome drug resistance and replace less efficacious treatments. In theory, knowledge of the entire genome of a pathogen identifies every potential drug target in any given microbe. In practice, the sheer complexity and the inadequate or inaccurate annotation of genomic information makes target identification and selection somewhat more difficult. Analysis of metabolic pathways provides a useful conceptual framework for the identification of potential drug targets and also for improving our understanding of microbial responses to nutritional, chemical and other environmental stresses. A number of metabolic databases are available as tools for such analyses. The strengths and weaknesses of this approach are discussed.

scholarly journals Using gene networks to drug target identification

2005 ◽  
Vol 2 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Zhenran Jiang ◽  
Yanhong Zhou
Keyword(s):  
Gene Networks ◽  
Drug Targets ◽  
Gene Network ◽  
Target Identification ◽  
Biological Data ◽  
Potential Drug ◽  
Drug Target Identification ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

Abstract The complete genome sequences have provided a plethora of potential drug targets. Gene network technique holds the promise of providing a conceptual framework for analysis of the profusion of biological data being generated on potential drug targets and providing insights to understand the biological regulatory mechanisms in diseases, which are playing an increasingly important role in searching for novel drug targets from the information contained in genomics. In this paper, we discuss some of the network-based approaches for identifying drug targets, with the emphasis on the gene network strategy. In addition, some of the relevant data resources and computational tools are given.

scholarly journals Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach

2020 ◽  
Vol 7 (3) ◽  
pp. 129
Author(s):  
Abid Ali ◽  
Shabir Ahmad ◽  
Abdul Wadood ◽  
Ashfaq U. Rehman ◽  
Hafsa Zahid ◽  
...  
Keyword(s):  
Drug Targets ◽  
Effective Control ◽  
Potential Drug ◽  
Homologous Proteins ◽  
Vaccine Candidates ◽  
Target Proteins ◽  
Subtractive Proteomics ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and veterinary health sectors. The identification of putative drug targets and vaccine candidates is crucial to control TBPs. No information has been recorded on designing novel drug targets and vaccine candidates based on proteins. Subtractive proteomics is an in silico approach that utilizes extensive screening for the identification of novel drug targets or vaccine candidates based on the determination of potential target proteins available in a pathogen proteome that may be used effectively to control diseases caused by these infectious agents. The present study aimed to investigate novel drug targets and vaccine candidates by utilizing subtractive proteomics to scan the available proteomes of TBPs and predict essential and non-host homologous proteins required for the survival of these diseases causing agents. Subtractive proteome analysis revealed a list of fifteen essential, non-host homologous, and unique metabolic proteins in the complete proteome of selected pathogens. Among these therapeutic target proteins, three were excluded due to the presence in host gut metagenome, eleven were found to be highly potential drug targets, while only one was found as a potential vaccine candidate against TBPs. The present study may provide a foundation to design potential drug targets and vaccine candidates for the effective control of infections caused by TBPs.

Potential Drug Targets Identification against Clostridioides difficile (CD) and Characterization of Indispensable Proteins by a Subtractive Genomics Approach Followed by Virtual Screening

2021 ◽  
Vol 18 ◽  
Author(s):  
Reaz Uddin ◽  
Alina Arif
Keyword(s):  
Drug Targets ◽  
Drug Resistant ◽  
Potential Drug ◽  
Drug Candidates ◽  
Subtractive Genomics ◽  
Clostridioides Difficile ◽  
Subtractive Genomics Approach ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

Background: Clostridioides difficile (CD) is a multi-drug resistant, enteric pathogenic bacterium. The CD associated infections are the leading cause of nosocomial diarrhea that can further lead to pseudomembranous colitis up to a toxic mega-colon or sepsis with greater mortality and morbidity risks. The CD infection possess higher rates of recurrence due to its greater resistance against antibiotics. Considering its higher rates of recurrence, it has become a major burden on the healthcare facilities. Therefore, there is a dire need to identify novel drug targets to combat with the antibiotic resistance of Clostridioides difficile. Objective: To identify and propose new and novel drug targets against the Clostridioides difficile. Methods: In the current study, a computational subtractive genomics approach was applied to obtain a set of potential drug targets that exists in the multi-drug resistant strain of Clostridioides difficile. Here, the uncharacterized proteins were studied as potential drug targets. The methodology involved several bioinformatics databases and tools. The druggable proteins sequences were retrieved based on non-homology with host proteome and essentiality for the survival of the pathogen. The uncharacterized proteins were functionally characterized using different computational tools and sub-cellular localization was also predicted. The metabolic pathways were analyzed using KEGG database. Eventually, the druggable proteome has been fetched using sequence similarity with the already available drug targets present in DrugBank database. These druggable proteins were further explored for the structural details to identify drug candidates. Results : A priority list of potential drug targets was provided with the help of the applied method on complete proteome set of the C. difficile. Moreover, the drug like compounds have been screened against the potential drug targets to prioritize potential drug candidates. To facilitate the need for drug targets and therapies, the study proposed five potential protein drug targets out of which three proposed drug targets were subjected to homology modeling to explore their structural and functional activities. Conclusion: In conclusion, we proposed three unique, unexplored drug targets against C. difficile. The structure-based methods were applied and resulted in a list of top scoring compounds as potential inhibitors to proposed drug targets.

Identification of Glucose-Dependent Insulin Secretion Targets in Pancreatic β Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing

2008 ◽  
Vol 13 (2) ◽  
pp. 128-134 ◽  
Author(s):  
Weizhen Wu ◽  
Jin Shang ◽  
Yue Feng ◽  
Chris M. Thompson ◽  
Sarah Horwitz ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Drug Targets ◽  
Target Identification ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Major Bottleneck ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

Identification and validation of novel drug targets continues to be a major bottleneck in drug development, particularly for polygenic complex diseases such as type 2 diabetes. Here, the authors describe an approach that allows researchers to rapidly identify and validate potential drug targets by combining chemical tools and RNA interference technology. As a proof-of-concept study, the known mechanism Sigma LOPAC library was used to screen for glucose-dependent insulin secretion (GDIS) in INS-1 832/13 cells. In addition to several mechanisms that are known to regulate GDIS (such as cyclic adenosine monophosphate—specific phosphodiesterases, adrenoceptors, and Ca2+ channels), the authors find that several of the dopamine receptor ( DRD) antagonists significantly enhance GDIS, whereas DRD agonists profoundly inhibit GDIS. Subsequent siRNA studies in the same cell line indicate that knockdown of DRD2 enhanced GDIS. Furthermore, selective DRD2 antagonists and agonists also enhance or suppress, respectively, GDIS in isolated rat islets. The data support that the approach described here offers a rapid and effective way for target identification and validation. ( Journal of Biomolecular Screening 2008;128-134)

scholarly journals IN SILICO IDENTIFICATION OF NOVEL DRUG TARGETS IN ACINETOBACTER BAUMANNII BY SUBTRACTIVE GENOMIC APPROACH

2018 ◽  
Vol 11 (3) ◽  
pp. 230 ◽  
Author(s):  
Meenu Goyal ◽  
Citu Citu ◽  
Nidhi Singh
Keyword(s):  
Acinetobacter Baumannii ◽  
In Silico ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Potential Drug ◽  
Homologous Proteins ◽  
Essential Proteins ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

 Objective: Multiple drug resistance (MDR) in bacteria, particularly Gram-negative bacilli, has significantly hindered the treatment of infections caused by these bacteria. This results in the need for identifying new drugs and drug targets for these bacteria. The objective of this study was to identify novel drug targets in Acinetobacter baumannii which has emerged as a medically important pathogen due to an increasing number of infections caused by it and its MDR property.Methods: In our study, we implemented in silico subtractive genomics approach to identify novel drug targets in A. baumannii American type culture collection 17978. Various databases and online software were used to build a systematic workflow involving comparative genomics, metabolic pathways analysis, and drug target prioritization to identify pathogen-specific novel drug targets.Results: First, 458 essential proteins were retrieved from a database of essential genes, and by performing BLASTp against Homo sapiens, 246 human non-homologous essential proteins were selected of 458 proteins. Metabolic pathway analysis performed by Kyoto Encyclopedia of Genes and Genomes–Kyoto Automatic Annotation Server revealed that these 246 essential non-homologous proteins were involved in 66 metabolic pathways. Among these metabolic pathways, 12 pathways were found to be unique to Acinetobacter that involved 37 non-homologous essential proteins. Of these essential non-homologous proteins, 19 proteins were found in common as well as unique metabolic pathways and only 18 proteins were unique to Acinetobacter. Finally, these target proteins were filtered to 9 potential targets, based on subcellular localization and assessment of druggability using Drug bank, ChEMBL, and literature.Conclusion: Our study identified nine potential drug targets which are novel targets in A. baumannii and can be used for designing drugs against these proteins. These drugs will be pathogen specific with no side effects on human host, as the potential drug targets are human non-homologous.

scholarly journals Drug Target Prediction Based on the Herbs Components: The Study on the Multitargets Pharmacological Mechanism of Qishenkeli Acting on the Coronary Heart Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yong Wang ◽  
Zhongyang Liu ◽  
Chun Li ◽  
Dong Li ◽  
Yulin Ouyang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Angiotensin Ii ◽  
Drug Target ◽  
Drug Targets ◽  
Target Prediction ◽  
Coronary Artery Ligation ◽  
Potential Drug ◽  
Drug Target Prediction ◽  
Potential Drug Targets

In this paper, we present a case study of Qishenkeli (QSKL) to research TCM’s underlying molecular mechanism, based on drug target prediction and analyses of TCM chemical components and following experimental validation. First, after determining the compositive compounds of QSKL, we use drugCIPHER-CS to predict their potential drug targets. These potential targets are significantly enriched with known cardiovascular disease-related drug targets. Then we find these potential drug targets are significantly enriched in the biological processes of neuroactive ligand-receptor interaction, aminoacyl-tRNA biosynthesis, calcium signaling pathway, glycine, serine and threonine metabolism, and renin-angiotensin system (RAAS), and so on. Then, animal model of coronary heart disease (CHD) induced by left anterior descending coronary artery ligation is applied to validate predicted pathway. RAAS pathway is selected as an example, and the results show that QSKL has effect on both rennin and angiotensin II receptor (AT1R), which eventually down regulates the angiotensin II (AngII). Bioinformatics combing with experiment verification can provide a credible and objective method to understand the complicated multitargets mechanism for Chinese herbal formula.

scholarly journals In Silico identification of potential drug targets by subtractive genome analysis of Enterococcus faecium DO

2020 ◽  
Author(s):  
Marwah Karim ◽  
MD Nazrul Islam ◽  
G. M. Nurnabi Azad Jewel
Keyword(s):  
Alcohol Dehydrogenase ◽  
Enterococcus Faecium ◽  
In Silico ◽  
Drug Targets ◽  
3D Structure ◽  
Comparative Genomic ◽  
Therapeutic Drug ◽  
Potential Drug ◽  
Novel Drug ◽  
Potential Drug Targets

AbstractOnce believed to be a commensal bacteria, Enterococcus faecium has recently emerged as an important nosocomial pathogen worldwide. A recent outbreak of E. faecium unrevealed natural and in vitro resistance against a myriad of antibiotics namely ampicillin, gentamicin and vancomycin due to over-exposure of the pathogen to these antibiotics. This fact combined with the ongoing threat demands the identification of new therapeutic targets to combat E. faecium infections.In this present study, comparative proteome analysis, subtractive genomic approach, metabolic pathway analysis and additional drug prioritizing parameters were used to propose a potential novel drug targets for E. faecium strain DO. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified a total of 207 putative target proteins in E. faecium DO that showed no similarity to human proteins. Among them 105 proteins were identified as essential novel proteins that could serve as potential drug targets through further bioinformatic approaches; such as-prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characterization. Eventually 19 non-homologous essential proteins of E. faecium DO were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets. Among these targets aldehyde-alcohol dehydrogenase was found to be involved in maximum pathways, and therefore, was chosen as novel drug target. Interestingly, aldehyde-alcohol dehydrogenase enzyme contains two domains namely acetaldehyde dehydrogenase and alcohol dehydrogenase, on which a 3D structure homology modeling and in silico molecular docking were performed. Finally, eight molecules were confirmed as the most suitable ligands for aldehyde-alcohol dehydrogenase and hence proposed as the potential inhibitors of this target.In conclusion, being human non-homologous, aldehyde-alcohol dehydrogenase protein can be targeted for potential therapeutic drug development in future. However, laboratory based experimental research should be performed to validate our findings in vivo.

scholarly journals “In Silico Metabolic Pathway Analysis and Docking Analysis of Treponema Pallidum Subs. Pallidum Nichols for Potential Drug Targets”

2017 ◽  
Vol 10 (5) ◽  
pp. 261
Author(s):  
Radha Mahendran
Keyword(s):  
Homology Modeling ◽  
Metabolic Pathway ◽  
Drug Targets ◽  
Active Sites ◽  
Homo Sapiens ◽  
Treponema Pallidum ◽  
Potential Drug ◽  
Metabolic Pathway Analysis ◽  
Docking Analysis ◽  
Potential Drug Targets

ABSTRACT Objective: Syphilis is a sexually transmitted infection caused by the spirochaete, Treponema pallidum subspecies pallidum nichols. In this study, a comparative metabolic pathway analysis and molecular docking was performed to identify putative drug targets.Methods: The biochemical pathways of Treponema pallidum subs. pallidum nichols and Homo sapiens were compared using KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway. The amino acid sequence of the selected enzymes were retrieved and Blastp was performed. Out of 9 enzymes, enolase was modeled using ModWeb and the structure was validated using RAMPAGE. The active sites were identified using Metapocket 2.0 and further docked using AutoDock 4.2.Results: The enzymes which were not similar to that of Homo sapiens were filtered out as potential drug targets. A total of 9 enzymes were retrieved which were present only in the Treponema pallidum subs. pallidum nichols. The structure obtained from Homology modeling was validated and further active sites were predicted. The docking analysis results showed the interaction between enolase and doxycycline and the structures were obtained using PyMol.Conclusion: Through this study, doxycycline which has antibacterial effect and a derivative of tetracycline could be one of the potential ligands. Keywords: Syphilis, Treponema pallidum, KEGG, Blastp, metabolic pathway, Homology Modeling, DockingREVIEWERSProf.G.SHOBA,Bioinformatics Department      Dr.M.G.R Janaki College of Arts and Science for Women      University of Madras      [email protected]      Phone: 9094009791 2. Prof .VINOTH,Biotechnology & Bioinformatics DepartmentHindustan University,Kelambakkam, Chennai-603103                  [email protected]                 Phone - + 91 97895 95766

scholarly journals D3Targets-2019-nCoV: A Web Server to Identify Potential Targets for Antivirals Against 2019-nCoV

2020 ◽  
Author(s):  
Yulong Shi ◽  
Xinben Zhang ◽  
Kaijie Mu ◽  
Cheng Peng ◽  
Zhengdan Zhu ◽  
...  
Keyword(s):  
Drug Target ◽  
Drug Targets ◽  
Underlying Mechanism ◽  
Modern Medicine ◽  
Potential Drug ◽  
Target Interaction ◽  
Human Proteins ◽  
Binding Pockets ◽  
Effective Drugs ◽  
Potential Drug Targets

<p>2019-nCoV has caused more than 560 deaths as of 6 February 2020 worldwide, mostly in China. Although there are no effective drugs approved, many clinical trials are incoming or ongoing in China which utilize traditional chinese medicine or modern medicine. Moreover, many groups are working on the cytopathic effect assay to fight against 2019-nCoV, which will result in compounds with good activity yet unknown targets. Identifying potential drug targets will be of great importance to understand the underlying mechanism of how the drug works. Here, we <a></a><a>compiled</a> the 3D structures of 17 2019-nCoV proteins and 3 related human proteins, which resulted in 208 binding pockets. Each submitted compound will be docked to these binding pockets by the docking software smina and the docking results will be presented in ascending order of compound-target interaction energy (kcal/mol). We hope the computational tool will shed some light on the potential drug target for the identified antivirals. D3Targets-2019-nCoV is available free of charge at https://www.d3pharma.com/D3Targets-2019-nCoV/D3Docking/index.php.</p>

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