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.

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.

scholarly journals Identification of a Novel Therapeutic Target against XDR Salmonella Typhi H58 Using Genomics Driven Approach Followed Up by Natural Products Virtual Screening

2021 ◽  
Vol 9 (12) ◽  
pp. 2512
Author(s):  
Khurshid Jalal ◽  
Kanwal Khan ◽  
Muhammad Hassam ◽  
Muhammad Naseer Abbas ◽  
Reaz Uddin ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Drug Targets ◽  
Salmonella Typhi ◽  
Drug Resistant ◽  
Acid Biosynthesis ◽  
New Drug ◽  
Subtractive Genomics ◽  
Colanic Acid ◽  
Novel Drug ◽  
Potential Drug Targets

Typhoid fever is caused by a pathogenic, rod-shaped, flagellated, and Gram-negative bacterium known as Salmonella Typhi. It features a polysaccharide capsule that acts as a virulence factor and deceives the host immune system by protecting phagocytosis. Typhoid fever remains a major health concern in low and middle-income countries, with an estimated death rate of ~200,000 per annum. However, the situation is exacerbated by the emergence of the extensively drug-resistant (XDR) strain designated as H58 of S. Typhi. The emergence of the XDR strain is alarming, and it poses serious threats to public health due to the failure of the current therapeutic regimen. A relatively newer computational method called subtractive genomics analyses has been widely applied to discover novel and new drug targets against pathogens, particularly drug-resistant ones. The method involves the gradual reduction of the complete proteome of the pathogen, leading to few potential and novel drug targets. Thus, in the current study, a subtractive genomics approach was applied against the Salmonella XDR strain to identify potential drug targets. The current study predicted four prioritized proteins (i.e., Colanic acid biosynthesis acetyltransferase wcaB, Shikimate dehydrogenase aroE, multidrug efflux RND transporter permease subunit MdtC, and pantothenate synthetase panC) as potential drug targets. Though few of the prioritized proteins are treated in the literature as the established drug targets against other pathogenic bacteria, these drug targets are identified here for the first time against S. Typhi (i.e., S. Typhi XDR). The current study aimed at drawing attention to new drug targets against S. Typhi that remain largely unexplored. One of the prioritized drug targets, i.e., Colanic acid biosynthesis acetyltransferase, was predicted as a unique, new drug target against S. Typhi XDR. Therefore, the Colanic acid was further explored using structure-based techniques. Additionally, ~1000 natural compounds were docked with Colanic acid biosynthesis acetyltransferase, resulting in the prediction of seven compounds as potential lead candidates against the S. Typhi XDR strain. The ADMET properties and binding energies via the docking program of these seven compounds characterized them as novel drug candidates. They may potentially be used for the development of future drugs in the treatment of Typhoid fever.

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 Virtual Screening and Docking Studies of Identified Potential Drug Target: Polysaccharide Deacetylase in Bacillus anthracis

2015 ◽  
Vol 34 ◽  
pp. 70-77
Author(s):  
K. Zaveri ◽  
A. Krishna Chaitanya ◽  
I. Bhaskar Reddy
Keyword(s):  
Virtual Screening ◽  
Bacillus Anthracis ◽  
Drug Target ◽  
Drug Targets ◽  
Docking Studies ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Subtractive Genomics ◽  
Subtractive Genomics Approach ◽  
Novel Drug

In recent years, insilico approaches have been predicting novel drug targets. The present day development in pharmaceutics mainly ponders on target based drugs and this has been aided by structure based drug designing and subtractive genomics. In the present study, the computational genome subtraction methodology was applied for identification of novel, potential drug target against Bacillus anthracis, cause of deadly anthrax. The potential drug target identified through subtractive genomics approach was considered as polysaccharide deacetylase. By virtual screening against NCI database and Drugbank chemical libraries, two potential lead molecules were predicted. Further the potential lead molecules and target protein were subjected for docking studies using Autodock.

THE MAGIC BULLETS AND TUBERCULOSIS DRUG TARGETS

2005 ◽  
Vol 45 (1) ◽  
pp. 529-564 ◽  
Author(s):  
Ying Zhang
Keyword(s):  
Drug Targets ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Drug Candidates ◽  
Resistant Tuberculosis ◽  
Conventional Drug ◽  
New Generation ◽  
Effective Drugs ◽  
Novel Drug ◽  
Novel Drug Targets

Modern chemotherapy has played a major role in our control of tuberculosis. Yet tuberculosis still remains a leading infectious disease worldwide, largely owing to persistence of tubercle bacillus and inadequacy of the current chemotherapy. The increasing emergence of drug-resistant tuberculosis along with the HIV pandemic threatens disease control and highlights both the need to understand how our current drugs work and the need to develop new and more effective drugs. This review provides a brief historical account of tuberculosis drugs, examines the problem of current chemotherapy, discusses the targets of current tuberculosis drugs, focuses on some promising new drug candidates, and proposes a range of novel drug targets for intervention. Finally, this review addresses the problem of conventional drug screens based on inhibition of replicating bacilli and the challenge to develop drugs that target nonreplicating persistent bacilli. A new generation of drugs that target persistent bacilli is needed for more effective treatment of tuberculosis.

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.

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