scholarly journals Identification of potential drug targets and vaccine candidates in Clostridium botulinum using subtractive genomics approach

2019 ◽  
Vol 15 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Rati Sudha ◽  
◽  
Amit Katiyar ◽  
Poonam Katiyar ◽  
Harpreet Singh ◽  
...  
Keyword(s):  
Clostridium Botulinum ◽  
Drug Targets ◽  
Potential Drug ◽  
Vaccine Candidates ◽  
Subtractive Genomics ◽  
Subtractive Genomics Approach ◽  
Potential Drug Targets

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 Genome Subtraction and Comparison for the Identification of Novel Drug Targets against Mycobacterium avium subsp. hominissuis

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 368 ◽  
Author(s):  
Reaz Uddin ◽  
Bushra Siraj ◽  
Muhammad Rashid ◽  
Ajmal Khan ◽  
Sobia Ahsan Halim ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
In Silico ◽  
Drug Targets ◽  
Mycobacterium Avium Subsp ◽  
Homology Search ◽  
Potential Drug ◽  
Subtractive Genomics ◽  
Complete Dataset ◽  
Subtractive Genomics Approach ◽  
Potential Drug Targets

Mycobacterium avium complex (MAC) is a major cause of non-tuberculous pulmonary and disseminated diseases worldwide, inducing bronchiectasis, and affects HIV and immunocompromised patients. In MAC, Mycobacterium avium subsp. hominissuis is a pathogen that infects humans and mammals, and that is why it is a focus of this study. It is crucial to find essential drug targets to eradicate the infections caused by these virulent microorganisms. The application of bioinformatics and proteomics has made a significant impact on discovering unique drug targets against the deadly pathogens. One successful bioinformatics methodology is the use of in silico subtractive genomics. In this study, the aim was to identify the unique, non-host and essential protein-based drug targets of Mycobacterium avium subsp. hominissuis via in silico a subtractive genomics approach. Therefore, an in silico subtractive genomics approach was applied in which complete proteome is subtracted systematically to shortlist potential drug targets. For this, the complete dataset of proteins of Mycobacterium avium subsp. hominissuis was retrieved. The applied subtractive genomics method, which involves the homology search between the host and the pathogen to subtract the non-druggable proteins, resulted in the identification of a few prioritized potential drug targets against the three strains of M. avium subsp. Hominissuis, i.e., MAH-TH135, OCU466 and A5. In conclusion, the current study resulted in the prioritization of vital drug targets, which opens future avenues to perform structural as well as biochemical studies on predicted drug targets against M. avium subsp. hominissuis.

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.

Strategies to Control Human Lymphatic Filarial Infection: Tweaking Host’s Immune System

2019 ◽  
Vol 19 (14) ◽  
pp. 1226-1240 ◽  
Author(s):  
Puvvada Kalpana Murthy
Keyword(s):  
Drug Targets ◽  
Parasitic Infection ◽  
Wuchereria Bancrofti ◽  
Immune Competence ◽  
Potential Drug ◽  
Filarial Infection ◽  
Alternative Strategies ◽  
Vaccine Candidates ◽  
Potential Drug Targets ◽  
Made In

Human lymphatic filariasis (LF), a parasitic infection caused by the nematodes Wuchereria bancrofti, Brugia malayi and B. timori, and transmitted by mosquito, results in a debilitating disease commonly identified as ‘elephantiasis’. LF affects millions of people in India and several other tropical and sub-tropical countries imposing a huge economic burden on governments due to disability associated loss of man-hours and for disease management. Efforts to control the infection by WHO’s mass drug administration (MDA) strategy using three antifilarials diethylcarbamazine, albendazole and ivermectin are only partly successful and therefore, there is an immediate need for alternative strategies. Some of the alternative strategies being explored in laboratories are: enhancing the immune competence of host by immunomodulation, combining immunomodulation with antifilarials, identifying immunoprophylactic parasite molecules (vaccine candidates) and identifying parasite molecules that can be potential drug targets. This review focuses on the advances made in this direction.

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.

scholarly journals Mining the Proteome of Haemophilus ducreyi for Identification of Potential Drug Targets

2010 ◽  
Vol 4 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Aditya Narayan Sarangi ◽  
Stuti Gupta ◽  
Nidhi Trivedi ◽  
Bhawna Rathi ◽  
Shailendra Kumar Gupta
Keyword(s):  
Drug Targets ◽  
Hiv Transmission ◽  
Transmitted Disease ◽  
Haemophilus Ducreyi ◽  
Potential Drug ◽  
Vaccine Candidates ◽  
Sexually Transmitted ◽  
Essential Proteins ◽  
Potential Vaccine ◽  
Potential Drug Targets

Chancroid is an extremely infectious sexually transmitted disease (STD) caused by the bacterium Haemophilus ducreyi, prevalent in Africa, United States and in some parts of South Asia. Chancroid has been recognized as a cofactor for human immunodeficiency virus (HIV) transmission. So, there is a requirement to develop an efficient drug to combat chancroid, which can also diminish the HIV prevalence in those populations where chancroid is a prime source for HIV infection. The availability of the complete proteome information of H. ducreyi help enabled in silico analysis for identification of potential vaccine candidates and drug targets. Our study revealed 1226 proteins in H. ducreyi to be nonhomologous with human proteome. Screening these proteins using the Database of Essential Genes (DEG) resulted in the identification of 451 essential proteins. Analysis of the identified essential proteins, using the KEGG Automated Annotation Server (KAAS), revealed 40 proteins of H. ducreyi as potential drug targets as they are involved in pathogen specific metabolic pathways. Subcellular localization prediction of these 451 essential proteins revealed that 11 proteins lie on the outer membrane of the pathogen which could be potential vaccine candidates. Functional family prediction for the 50 putative uncharacterized essential proteins of H. ducreyi by SVM-Prot web server revealed that out of 50, 3 proteins as transmembrane proteins, which may be potential drug targets. Identification of potential inhibitors against these targets through virtual screening may consequence in detection of novel lead compounds effective against H. ducreyi to combat chancroid.

Sign in / Sign up

Export Citation Format

Share Document