scholarly journals Potential Drug Target Identification of Legionella pneumophila by Subtractive Genome Analysis: An In Silico Approach

2019 ◽  
Vol 35 (2) ◽  
pp. 102-107
Author(s):  
Md Sadikur Rahman Shuvo ◽  
Shahriar Kabir Shakil ◽  
Firoz Ahmed
Keyword(s):  
Legionella Pneumophila ◽  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Genomic Analysis ◽  
Opportunistic Pathogen ◽  
Surface Proteins ◽  
Multi Drug Resistance ◽  
Therapeutic Drug ◽  
Homologous Proteins ◽  
Essential Proteins

Though Legionella pneumophila is an opportunistic pathogen, recent reports about multi drug resistance in L. pneumophila is alarming. Annotated whole genome provides a pool of information which is applied for therapeutic drug targets identification in pathogenic bacteria. Subtractive genomic analysis is a pragmatic approach to screen the essential proteins present in pathogen but absent in host. Phylogenetically closely related L. pneumophila str. Philadelphia and L. pneumophila str. ATCC43209 protein profiles were analyzed to identify putative drug targets. Paralogous duplicate profiles were primarily discarded using CD-hit suit. Six hundred and ninety one L. pneumophila str. Philadelphia and 690 L. pneumophila str. ATCC43209 human homologous proteins were excluded using blstP. Among the human non-homologous proteins, the essential proteins for bacteria were separated using DEG tool. For both strains, one hundred and nineteen essential proteins were marked which participate in various metabolic pathways. Among them 11 unique proteins were found. Beside it, 15 and 16 exposed surface proteins were present in strain Philadelphia and ATCC43209 respectively. These unique and cell surface proteins can be utilized for effective drug and vaccine targets. Bangladesh J Microbiol, Volume 35 Number 2 December 2018, pp 102-107

Proteome Mining for the Identification of Putative Drug Targets For Human Pathogen Clostridium Tetani

2019 ◽  
Vol 14 (6) ◽  
pp. 532-540 ◽  
Author(s):  
Anum Munir ◽  
Shaukat Iqbal Malik ◽  
Khalid Akhtar Malik
Keyword(s):  
Drug Targets ◽  
Cellular Localization ◽  
Pathogenic Bacteria ◽  
Homo Sapiens ◽  
Proteome Analysis ◽  
Essential Genes ◽  
Homologous Proteins ◽  
Clostridium Tetani ◽  
Essential Proteins ◽  
Localization Analysis

Background: Clostridium tetani are rod-like, anaerobic types of pathogenic bacteria of the genus Clostridium. It is Gram-positive in nature and appears as a tennis racket or drumsticks on staining with the dye. Tetanus is a neuromuscular disease wherein the Clostridium tetani exotoxin produces muscle fits in the host. Tetanus is the second leading cause of worldwide deaths occurring from the family of immunization-preventable diseases. Methods: In this research, subtractive proteome analysis of C. tetani was performed to identify putative drug targets. The proteins were subjected to blast analysis against Homo sapiens to exclude homologous proteins. The database of Essential Genes was used to determine the essential proteins of the pathogen. These basic proteins were additionally analyzed to anticipate the corresponding metabolic pathways. Results: Cellular localization analysis was carried out to determine the possibility of the protein presence in the outer membrane. The study has recognized 29 essential genes and 20 unique pathways of 2314 proteins as potential drug targets. There are 29 essential proteins, out of which, 3 membrane proteins were also identified as putative drug targets. Conclusion: Virtual screening in contrast to these proteins can be valuable in the identification of novel clinical compounds for the C. tetani infections in Homo sapiens.

Proteome wide screening for identification of putative drug target gene in Nautella italica and structure-based ligand screening for therapeutic candidates

2021 ◽  
Vol 25 (12) ◽  
pp. 122-136
Author(s):  
Odumpatta Rajasree ◽  
Arumugam Mohanapriya
Keyword(s):  
Drug Target ◽  
Drug Targets ◽  
Three Dimensional ◽  
Opportunistic Pathogen ◽  
Dimensional Structure ◽  
Therapeutic Drug ◽  
Zinc Database ◽  
Delisea Pulchra ◽  
Toxicity Analysis ◽  
Potential Ligand

In silico based subtractive genomic approaches were employed to identify the key drug targets for an opportunistic pathogen Nautella italica, a member of the marine Roseobacter clade that causes bleaching disease in the temperate-marine red macro algae, Delisea pulchra. The aim of this study is to propose new active ligands against bleaching disease seen in algae. Using comparative and subtractive genomic approach, a set of 21 proteins were identified as the therapeutic drug target proteins for algal bleaching. This core set of drug targets has been analyzed for network topology using string network analysis and major hub gene identified by CytoHubba was rpoB (DNA directed RNA Polymerase subunit beta). The three-dimensional structure of rpoB was built by comparative modelling and used to perform a virtual screening of Zinc database by DOCK Blaster server. The 50 top scored compounds were screened for toxicity analysis by OSIRIS Data Warrior and ECOSAR tool. Further refinement by autodock program revealed two compounds ZINC49821385 and ZINC97218938 with the best binding energy of -7.07 and -6.79 respectively. These results indicated that 5-(4- isopropylphenyl)furan-2-carboxamide (ZINC ID 49821385) could be one of the potential ligand to treat bleaching disease in algae.

scholarly journals Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in Mycoplasma genitalium

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 921
Author(s):  
Abiodun Joseph Fatoba ◽  
Moses Okpeku ◽  
Matthew Adekunle Adeleke
Keyword(s):  
Metabolic Pathways ◽  
Drug Targets ◽  
Mycoplasma Genitalium ◽  
Therapeutic Drug ◽  
Homologous Proteins ◽  
Subtractive Genomics ◽  
Cytoplasmic Proteins ◽  
Novel Drug ◽  
Novel Drug Targets ◽  
Novel Therapeutic

Mycoplasma genitalium infection is a sexually transmitted infection that causes urethritis, cervicitis, and pelvic inflammatory disease (PID) in men and women. The global rise in antimicrobial resistance against recommended antibiotics for the treatment of M. genitalium infection has triggered the need to explore novel drug targets against this pathogen. The application of a bioinformatics approach through subtractive genomics has proven highly instrumental in predicting novel therapeutic targets against a pathogen. This study aimed to identify essential and non-homologous proteins with unique metabolic pathways in the pathogen that could serve as novel drug targets. Based on this, a manual comparison of the metabolic pathways of M. genitalium and the human host was done, generating nine pathogen-specific metabolic pathways. Additionally, the analysis of the whole proteome of M. genitalium using different bioinformatics databases generated 21 essential, non-homologous, and cytoplasmic proteins involved in nine pathogen-specific metabolic pathways. The further screening of these 21 cytoplasmic proteins in the DrugBank database generated 13 druggable proteins, which showed similarity with FDA-approved and experimental small-molecule drugs. A total of seven proteins that are involved in seven different pathogen-specific metabolic pathways were finally selected as novel putative drug targets after further analysis. Therefore, these proposed drug targets could aid in the design of potent drugs that may inhibit the functionality of these pathogen-specific metabolic pathways and, as such, lead to the eradication of this pathogen.

scholarly journals Subtractive Genomic Analysis for Identification of Novel Drug Targets and Vaccine Candidates against Bartonella bacilliformis subsp. Ver097

2019 ◽  
Author(s):  
Md. Tahsin Khan ◽  
Araf Mahmud ◽  
Md. Asif Iqbal ◽  
Mahmudul Hasan
Keyword(s):  
Drug Targets ◽  
Neglected Tropical Diseases ◽  
Genomic Analysis ◽  
Homologous Proteins ◽  
Bartonella Bacilliformis ◽  
Efficient Treatment ◽  
Flagellar Biosynthesis ◽  
Therapeutic Compounds ◽  
Novel Drug ◽  
Novel Drug Targets

AbstractBartonella bacilliformis is the causative agent of Carrión’s disease, one of the truly neglected tropical diseases found in Peru, Colombia and Ecuador. Recent evidence predicts that Bartonella bacilliformis subsp. ver097 can emerge as an antibacterial resistant strain and hence identification of novel drug targets is a crying need. Subtractive genome analysis of B. bacilliformis subsp. ver097 was successfully done in order to address the challenges. Various computational tools and online based servers were used to screen out human homologous proteins of pathogen and proteins involved in common metabolic pathways of host and pathogen. Only 7 proteins involved in pathogen specific pathways were further analyzed to identify membrane proteins. ‘Flagellar biosynthesis protein FlhA’ and ‘ABC transporter permease’ were found to be novel as targets according to DrugBank database. To avoid side effects in human while administering drugs, human ‘anti-targets’ analysis was performed to confirm non-homology of selected novel drug targets. Both predicted proteins also showed probability of antigenicity prediction through VaxiJen, however, ‘Flagellar biosynthesis protein FlhA’ showed broad spectrum conservancy with Bartonella strains. Therefore, Flagellar biosynthesis protein FlhAcould facilitate the development of novel drugs and therapeutic compounds along with vaccines for efficient treatment of infections caused by Bartonella bacilliformis subsp. ver097.

scholarly journals Analyzing the Essential Proteins Set of Plasmodium Falciparum PF3D7 for Novel Drug Targets Identification Against Malaria

2021 ◽  
Author(s):  
Fawad Ali ◽  
Hira Wali ◽  
Saadia Jan ◽  
Muneeba Aslam ◽  
Imtiaz Ahmad ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Protein Interactions ◽  
Drug Targets ◽  
Human Life ◽  
Multi Drug Resistance ◽  
Essential Proteins ◽  
Human Host

Abstract Background: Plasmodium falciparum is an obligate intracellular parasite of humans that causes malaria. P. falciparum is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance of P. falciparum is rapidly increasing. There is a need to address new anti-malarial therapeutics strategies to combat the drug-resistance threat.Methods: We retrieved the P. falciparum essential proteins from the recently published studies. Pathogen essential proteins were initially scanned against human host and its gut microbiome proteome sets by comparative proteomics analyses. The human host non-homologs essential proteins of P. falciparum were additionally analyzed for druggability potential via in silico methods to possibly identify novel therapeutic targets.Results: The analyses identified six P. falciparum essential and human host non-homolog proteins that follow the key druggability features. These druggable targets have not catalogued so far in the Drugbank repository. These prioritized proteins seem novel and promising drug targets against P. falciparum due to their key protein-protein interactions features in pathogen-specific biological pathways and to hold appropriate drug-like molecule binding pockets. Conclusion: The prioritized protein targets may worthy to test in malarial drug discovery program to overcome the anti-malarial resistance issues. The in-vitro and in-vivo studies might be promising for additional validation of these prioritized lists of drug targets against malaria.

scholarly journals Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fawad Ali ◽  
Hira Wali ◽  
Saadia Jan ◽  
Asad Zia ◽  
Muneeba Aslam ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Virtual Screening ◽  
Drug Targets ◽  
Human Life ◽  
Multi Drug Resistance ◽  
Essential Proteins ◽  
Human Host

Abstract Background Plasmodium falciparum is an obligate intracellular parasite of humans that causes malaria. Falciparum malaria is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance of P. falciparum is rapidly increasing. There is a need to address new anti-malarial therapeutics strategies to combat the drug-resistance threat. Methods The P. falciparum essential proteins were retrieved from the recently published studies. These proteins were initially scanned against human host and its gut microbiome proteome sets by comparative proteomics analyses. The human host non-homologs essential proteins of P. falciparum were additionally analysed for druggability potential via in silico methods to possibly identify novel therapeutic targets. Finally, the PfAp4AH target was prioritized for pharmacophore modelling based virtual screening and molecular docking analyses to identify potent inhibitors from drug-like compounds databases. Results The analyses identified six P. falciparum essential and human host non-homolog proteins that follow the key druggability features. These druggable targets have not been catalogued so far in the Drugbank repository. These prioritized proteins seem novel and promising drug targets against P. falciparum due to their key protein–protein interactions features in pathogen-specific biological pathways and to hold appropriate drug-like molecule binding pockets. The pharmacophore features based virtual screening of Pharmit resource predicted a lead compound i.e. MolPort-045–917-542 as a promising inhibitor of PfAp4AH among prioritized targets. Conclusion The prioritized protein targets may worthy to test in malarial drug discovery programme to overcome the anti-malarial resistance issues. The in-vitro and in-vivo studies might be promising for additional validation of these prioritized lists of drug targets against malaria.

Subtractive Proteome Mining Approach Towards Unique Putative Drug Targets Identification for Salmonella Typhimurium

2019 ◽  
Vol 19 ◽  
Author(s):  
Rabia Iftikhar ◽  
Muhammad Rizwan ◽  
Sajid Khan ◽  
Azhar Mehmood ◽  
Anum Munir
Keyword(s):  
Salmonella Typhimurium ◽  
Drug Targets ◽  
Homo Sapiens ◽  
Essential Genes ◽  
Intestinal Lumen ◽  
Homologous Proteins ◽  
Essential Proteins ◽  
Contaminated Food ◽  
Potential Drug Targets ◽  
Infants And Young Children

: Salmonella typhimurium is rod-shaped bacteria with a Gram-negative genus, belonging to the Enterobacteriaceae family of microbes, invades the intestinal lumen of Human. Salmonella typhimurium is a root source, accounting for gastroenteritis in humans as well as in other mammals. Gastroenteritisis associated with Salmonella Typhimurium by interacting with the contaminated food and water, spread to nearby people in the area. Small intestines are attacked by Salmonella and then enter into the bloodstream momentarily, and are responsible for millions of mortalities and morbidities around the globe. Salmonella typhimurium toxins cause gastrointestiritis due to inflammation in the stomach and intestine in infants and young children. It accounts for millions of deaths with a higher incidence rate in developing countries. Methods: : In the current research, subtractive proteome mining has been done to recognize putative drug targets. The proteome was analyzed through blast in order to exclude homologous proteins. Bacterial essential proteins were predicted and the participation of the essential genes in the metabolic pathways has been analyzed. Results: : 36 essential genes and 15 unique pathways have been identified as potential drug targets among the total of 1934 proteins. The location of proteins is determined as an outer membrane. 3 proteins out of 36 essential proteins are recognized as putative drug targets. Conclusion:: In the future, virtual screening for the evaluation of novel clinical compounds for the identified proteins is effective and valuable for Salmonella Typhimurium infection in Homo sapiens.

scholarly journals Subtractive genomics and molecular docking approach to identify drug targets against Stenotrophomonas maltophilia

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261111
Author(s):  
Hira Saleem ◽  
Usman Ali Ashfaq ◽  
Habibullah Nadeem ◽  
Muhammad Zubair ◽  
Muhammad Hussnain Siddique ◽  
...  
Keyword(s):  
Drug Targets ◽  
Stenotrophomonas Maltophilia ◽  
Acyl Carrier Protein ◽  
Multiple Drug Resistance ◽  
New Drugs ◽  
Multiple Drug ◽  
Carrier Protein ◽  
Homologous Proteins ◽  
Essential Proteins ◽  
Validation Experiment

Stenotrophomonas maltophilia is a multidrug resistant pathogen associated with high mortality and morbidity in patients having compromised immunity. The efflux systems of S. maltophilia include SmeABC and SmeDEF proteins, which assist in acquisition of multiple-drug-resistance. In this study, proteome based mapping was utilized to find out the potential drug targets for S. maltophilia strain k279a. Various tools of computational biology were applied to remove the human-specific homologous and pathogen-specific paralogous sequences from the bacterial proteome. The CD-HIT analysis selected 4315 proteins from total proteome count of 4365 proteins. Geptop identified 407 essential proteins, while the BlastP revealed approximately 85 non-homologous proteins in the human genome. Moreover, metabolic pathway and subcellular location analysis were performed for essential bacterial genes, to describe their role in various cellular processes. Only two essential proteins (Acyl-[acyl-carrier-protein]—UDP-N acetyl glucosamine O-acyltransferase and D-alanine-D-alanine ligase) as candidate for potent targets were found in proteome of the pathogen, in order to design new drugs. An online tool, Swiss model was employed to model the 3D structures of both target proteins. A library of 5000 phytochemicals was docked against those proteins through the molecular operating environment (MOE). That resulted in to eight inhibitors for both proteins i.e. enterodiol, aloin, ononin and rhinacanthinF for the Acyl-[acyl-carrier-protein]—UDP-N acetyl glucosamine O-acyltransferase, and rhazin, alkannin beta, aloesin and ancistrocladine for the D-alanine-D-alanine ligase. Finally the ADMET was done through ADMETsar. This study supported the development of natural as well as cost-effective drugs against S. maltophilia. These inhibitors displayed the effective binding interactions and safe drug profiles. However, further in vivo and in vitro validation experiment might be performed to check their drug effectiveness, biocompatibility and their role as effective inhibitors.

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.

A Survey on Computational Methods for Essential Proteins and Genes Prediction

2019 ◽  
Vol 14 (3) ◽  
pp. 211-225 ◽  
Author(s):  
Ming Fang ◽  
Xiujuan Lei ◽  
Ling Guo
Keyword(s):  
Computational Methods ◽  
Drug Targets ◽  
Disease Genes ◽  
Essential Proteins ◽  
Experimental Identification ◽  
Cellular Life ◽  
Different Types ◽  
The Stability ◽  
Human Disease Genes ◽  
Biology Research

Background: Essential proteins play important roles in the survival or reproduction of an organism and support the stability of the system. Essential proteins are the minimum set of proteins absolutely required to maintain a living cell. The identification of essential proteins is a very important topic not only for a better comprehension of the minimal requirements for cellular life, but also for a more efficient discovery of the human disease genes and drug targets. Traditionally, as the experimental identification of essential proteins is complex, it usually requires great time and expense. With the cumulation of high-throughput experimental data, many computational methods that make useful complements to experimental methods have been proposed to identify essential proteins. In addition, the ability to rapidly and precisely identify essential proteins is of great significance for discovering disease genes and drug design, and has great potential for applications in basic and synthetic biology research. Objective: The aim of this paper is to provide a review on the identification of essential proteins and genes focusing on the current developments of different types of computational methods, point out some progress and limitations of existing methods, and the challenges and directions for further research are discussed.

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