scholarly journals RNA interference: what it is and what it does: A potent gene regulator

2004 ◽  
Vol 26 (5) ◽  
pp. 7-10
Author(s):  
Darcey Black ◽  
Sarah Newbury
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Rna Interference ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Human Cells ◽  
Potential Drug ◽  
Genetic Studies ◽  
Multicellular Organisms ◽  
Potential Drug Targets

RNA interference (RNAi) is a potent and specific way of down-regulating gene expression. It is effective in most multicellular organisms, and every gene in the genome can potentially be targeted, providing that the sequence of the gene is known. It has provided a breakthrough in the study of gene regulation, because the function of a gene can often be deduced by inhibiting its ex-pression. RNAi therefore provides a rapid way of studying the function of known genes in organisms where genetic studies are difficult. Since RNAi is effective in human cells, it is now being used in several ways. These include the elucidation of biochemical and metabolic pathways, validation of potential drug targets, and as a therapeutic in the treatment of disease.

METABOLIC PATHWAY ANALYSIS OFS. PNEUMONIAE: ANIN SILICOAPPROACH TOWARDS DRUG-DESIGN

2007 ◽  
Vol 05 (01) ◽  
pp. 135-153 ◽  
Author(s):  
SHAILZA SINGH ◽  
B. K. MALIK ◽  
D. K. SHARMA
Keyword(s):  
Drug Design ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Nucleotide Metabolism ◽  
Rational Drug Design ◽  
Systematic Evaluation ◽  
Potential Drug ◽  
Genome Database ◽  
Potential Drug Targets

The emergence of multidrug resistant varieties of Streptococcus pneumoniae (S. pneumoniae) has led to a search for novel drug targets. An in silico comparative analysis of metabolic pathways of the host Homo sapiens (H. sapiens) and the pathogen S. pneumoniae have been performed. Enzymes from the biochemical pathways of S. pneumoniae from the KEGG metabolic pathway database were compared with proteins from the host H. sapiens, by performing a BLASTp search against the non-redundant database restricted to the H. sapiens subset. The e-value threshold cutoff was set to 0.005. Enzymes, which do not show similarity to any of the host proteins, below this threshold, were filtered out as potential drug targets. Five pathways unique to the pathogen S. pneumoniae when compared to the host H. sapiens have been identified. Potential drug targets from these pathways could be useful for the discovery of broad-spectrum drugs. Potential drug targets were also identified from pathways related to lipid metabolism, carbohydrate metabolism, amino acid metabolism, energy metabolism, vitamin and cofactor biosynthetic pathways and nucleotide metabolism. Of the 161 distinct targets identified from these pathways, many are in various stages of progress at the Microbial Genome Database. However, 44 of the targets are new and can be considered for rational drug design. The study was successful in listing out potential drug targets from the S. pneumoniae proteome involved in vital aspects of the pathogen's metabolism, persistence, virulence and cell wall biosynthesis. This systematic evaluation of metabolic pathways of host and pathogen through reliable and conventional bioinformatics approach can be extended to other pathogens of clinical interest.

scholarly journals Discovery of “folded DNA” structures in human cells: Potential drug targets

2018 ◽  
Vol 44 (1) ◽  
pp. 125-128 ◽  
Author(s):  
Robert B. Raffa ◽  
Joseph V. Pergolizzi ◽  
Robert Taylor ◽  
Michael H. Ossipov ◽  
Keyword(s):  
Drug Targets ◽  
Human Cells ◽  
Potential Drug ◽  
Dna Structures ◽  
Potential Drug Targets

scholarly journals NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 904 ◽  
Author(s):  
Ángel Cores ◽  
Marta Piquero ◽  
Mercedes Villacampa ◽  
Rafael León ◽  
J. Carlos Menéndez
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Diseases ◽  
Protein Degradation ◽  
Phase Ii ◽  
Drug Targets ◽  
Antioxidant Response ◽  
Potential Drug ◽  
Critical Overview ◽  
Potential Drug Targets ◽  
Potential Use

NRF2 acts by controlling gene expression, being the master regulator of the Phase II antioxidant response, and also being key to the control of neuroinflammation. NRF2 activity is regulated at several levels, including protein degradation by the proteasome, transcription, and post-transcription. The purpose of this review is to offer a concise and critical overview of the main mechanisms of NRF2 regulation and their actual or potential use as targets for the treatment of neurodegenerative diseases.

scholarly journals Deciphering Potential Drug Targets in Clostridium Perfringens through Metabolic Pathway Analysis

2019 ◽  
pp. 432-437
Author(s):  
M Arockiyajainmary ◽  
Sivashankari Selvarajan
Keyword(s):  
Clostridium Perfringens ◽  
Pathway Analysis ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Cellular Localization ◽  
Potential Drug ◽  
Metabolic Pathway Analysis ◽  
Homologous Proteins ◽  
Potential Drug Targets

Background: In our day-to-day life, we are facing many dreadful diseases caused by many infectious pathogens. These pathogens invade the living organisms (host) and lethally damaging them. These dreadful pathogens were also be used as bioweapons. Among them, Clostridium perfringens is taken for the study. Clostridium perfringens is an anaerobic, rod shaped, gram positive bacteria capable of forming spores. It is prevalent in the environment and in the intestine of humans and other animals. It is the causative agent for a wide range of diseases including food borne diseases, gas gangrene and flesh eating disease called necrotizing fasciitis. C. perfringens is commonly found on raw meat and poultry that espouse to grow in conditions with very little or no oxygen, and under ideal conditions can multiply very rapidly. These conditions are occasionally lethal due to the substantial number of toxins such as alpha toxin, beta toxin, epsilon toxin and iota toxin produced by C. perfringens. It is significantly important to analyze the Drug targets of the pathogen in order to destroy them. Objective: The present work aims in identifying potential drug targets in C. perfringens through metabolic pathway analysis. Method: Primarily, the metabolic pathways of the host and pathogen are compared to identify unique pathways in the bacteria. Among the enzymes that catalyze unique metabolic pathways, the essential ones for the survival of the pathogen are identified. The druggability of the essential enzymes are predicted through identification of its sub cellular localization and other druggable parameters. Results: The comparative metabolic pathway analysis result shows that, among the 98 metabolic pathways of C.perfringens, 25 pathways were unique that they did not have a counterpart with Human. There were 113 enzymes involved in these unique pathways. The NCBI’s protein Blast search against human was done to identify the non-homologous proteins. There were 93 non-homologous proteins. Among the 93 non-homologous proteins, 47 proteins were found to be essential. Based on their sub-cellular localization, 32 proteins were identified as potential drug targets and 15 are probable vaccine candidates. Conclusion: The present work which started with 25 different pathways with more than a hundred different enzymes, resulted in the identification of 32 putative drug targets against C.perfringens infection. All these 32 identified targets did not have any human homolog and are highly essential for the survival of the organism. They were concluded as potential drug targets. Designing of compounds to inhibit these enzymes would be successful for treating the life threatening infections caused by this pathogen.

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.

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