scholarly journals Bioinformatics of thymidine metabolism in Trypanosoma evansi: exploring nucleoside deoxyribosyltransferase (NDRT) as a drug target

2021 ◽  
Author(s):  
Mahmoud Kandeel ◽  
Abdulla Al-Taher
Keyword(s):  
Drug Resistance ◽  
Metabolic Pathways ◽  
Drug Target ◽  
Drug Targets ◽  
Thymidine Phosphorylase ◽  
3D Structure ◽  
Protein Sequences ◽  
Trypanosoma Evansi ◽  
Discovery Process ◽  
Drug Discovery Process

Abstract Trypanosoma evansi, the causative agent of surra or camel trypanosomiasis, is characterized by the widest geographic distribution and host range among the known trypanosomes. Its zoonotic importance and increasing evidence of drug resistance necessitate the discovery of new drug targets. The drug discovery process entails finding an exploitable difference between the host and the parasite. In this study, the thymidine metabolic pathways in camel and T. evansi were compared by analyzing their metabolic maps, protein sequences, domain and motif contents, phylogenetic relationships, and 3D structure models. The two organisms were revealed to recycle thymidine differently: performed by thymidine phosphorylase in camels (Camelus genus), this role in T. evansi was associated with nucleoside deoxyribosyltransferase (NDRT), a unique trypanosomal enzyme absent in camels. Thymidine in T. evansi seems to be governed by thymine through NDRT, whereas in camels, thymidine can be produced from thymidylate via 5'-nucleotidase. As a result, NDRT may be a promising drug target against T. evansi.

scholarly journals Bioinformatics of Thymidine metabolism in camels and Trypanosoma evansi: nucleoside deoxyribosyltransferase (NDRT) as a drug target

2020 ◽  
Author(s):  
Mahmoud Kandeel ◽  
Abdulla Al-Taher
Keyword(s):  
Metabolic Pathways ◽  
Drug Target ◽  
Drug Targets ◽  
3D Structure ◽  
Trypanosoma Evansi ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Sequence Comparisons ◽  
Phylogenetic Relations ◽  
Interesting Difference

Abstract Background Trypanosoma evansi (T. evansi), the causative agent for surra or camel trypanosomiasis, is characterized by the widest geographic distribution and infects the widest range of hosts among the known trypanosomes. The recent zoonotic importance and increasing reports of drug resistance necessitate the discovery of new drug targets. Drug discovery process entails finding an interesting difference between the host and the parasite. Results In this study, the thymidine metabolic pathways were compared in camel and T. evansi. Metabolic maps, protein sequence comparisons, domain and motifs contents analysis, phylogenetic relations and 3D structure models were used in comparisons. A unique difference in thymidine metabolism was at the level of recycling of thymidine which was performed by thymidine phosphorylase in camel, while this role is T. evansi was associated with nucleoside deoxyribosyltransferase (NDRT), which is a unique enzyme for the trypanosome and was absent in camel. Thymidine in T. evansi seems to be governed by thymine through NDRT. In contrast to camel, in which thymidine can be produced from thymidylate by the action of 5'-nucleotidase. Conclusions NDRT can be regarded as a drug target against T. evansi for its strict presence in the parasite but not in the host.

scholarly journals Mycobacterium tuberculosis H37Rv: In Silico Drug Targets Identification by Metabolic Pathways Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Asad Amir ◽  
Khyati Rana ◽  
Arvind Arya ◽  
Neelesh Kapoor ◽  
Hirdesh Kumar ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
In Silico ◽  
Metabolic Pathways ◽  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Homo Sapiens ◽  
Protein Sequences ◽  
Mycobacterium Tuberculosis H37rv ◽  
Drug Molecules ◽  
Pathways Analysis

Mycobacterium tuberculosis (Mtb) is a pathogenic bacteria species in the genus Mycobacterium and the causative agent of most cases of tuberculosis. Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. This antibiotic resistance strain lead to development of the new antibiotics or drug molecules which can kill or suppress the growth of Mycobacterium tuberculosis. We have performed an in silico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen Mycobacterium tuberculosis (H37Rv). Novel efforts in developing drugs that target the intracellular metabolism of M. tuberculosis often focus on metabolic pathways that are specific to M. tuberculosis. We have identified five unique pathways for Mycobacterium tuberculosis having a number of 60 enzymes, which are nonhomologous to Homo sapiens protein sequences, and among them there were 55 enzymes, which are nonhomologous to Homo sapiens protein sequences. These enzymes were also found to be essential for survival of the Mycobacterium tuberculosis according to the DEG database. Further, the functional analysis using Uniprot showed involvement of all the unique enzymes in the different cellular components.

scholarly journals Exploring Drug Targets in Isoprenoid Biosynthetic Pathway forPlasmodium falciparum

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Tabish Qidwai ◽  
Farrukh Jamal ◽  
Mohd Y. Khan ◽  
Bechan Sharma
Keyword(s):  
Antimalarial Drug ◽  
Metabolic Pathways ◽  
Drug Target ◽  
Drug Targets ◽  
Malaria Parasite ◽  
Biosynthetic Pathway ◽  
Comprehensive Analysis ◽  
Isoprenoid Biosynthesis ◽  
Biosynthesis Pathway ◽  
Novel Targets

Emergence of rapid drug resistance to existing antimalarial drugs inPlasmodium falciparumhas created the need for prediction of novel targets as well as leads derived from original molecules with improved activity against a validated drug target. The malaria parasite has a plant plastid-like apicoplast. To overcome the problem of falciparum malaria, the metabolic pathways in parasite apicoplast have been used as antimalarial drug targets. Among several pathways in apicoplast, isoprenoid biosynthesis is one of the important pathways for parasite as its multiplication in human erythrocytes requires isoprenoids. Therefore targeting this pathway and exploring leads with improved activity is a highly attractive approach. This report has explored progress towards the study of proteins and inhibitors of isoprenoid biosynthesis pathway. For more comprehensive analysis, antimalarial drug-protein interaction has been covered.

scholarly journals A Comprehensive Review on Pharmacotherapeutics of Herbal Bioenhancers

2012 ◽  
Vol 2012 ◽  
pp. 1-33 ◽  
Author(s):  
Ghanshyam B. Dudhatra ◽  
Shailesh K. Mody ◽  
Madhavi M. Awale ◽  
Hitesh B. Patel ◽  
Chirag M. Modi ◽  
...  
Keyword(s):  
Drug Target ◽  
Oral Absorption ◽  
Experimental Studies ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Bioavailability Enhancement ◽  
Classical Text ◽  
Scientific Databases ◽  
Recent Advancement ◽  
Pharmaceutical Industries

In India, Ayurveda has made a major contribution to the drug discovery process with new means of identifying active compounds. Recent advancement in bioavailability enhancement of drugs by compounds of herbal origin has produced a revolutionary shift in the way of therapeutics. Thus, bibliographic investigation was carried out by analyzing classical text books and peer-reviewed papers, consulting worldwide-accepted scientific databases from last 30 years. Herbal bioenhancers have been shown to enhance bioavailability and bioefficacy of different classes of drugs, such as antibiotics, antituberculosis, antiviral, antifungal, and anticancerous drugs at low doses. They have also improved oral absorption of nutraceuticals like vitamins, minerals, amino acids, and certain herbal compounds. Their mechanism of action is mainly through absorption process, drug metabolism, and action on drug target. This paper clearly indicates that scientific researchers and pharmaceutical industries have to give emphasis on experimental studies to find out novel active principles from such a vast array of unexploited plants having a role as a bioavailability and bioefficacy enhancer. Also, the mechanisms of action by which bioenhancer compounds exert bioenhancing effects remain to be explored.

In-silico Subtractive Proteomic Analysis Approach for Therapeutic Targets in MDR Salmonella enterica subsp. enterica serovar Typhi str. CT18

2019 ◽  
Vol 19 (29) ◽  
pp. 2708-2717 ◽  
Author(s):  
Noor Rahman ◽  
Ijaz Muhammad ◽  
Gul E. Nayab ◽  
Haroon Khan ◽  
Rosanna Filosa ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Metabolic Pathways ◽  
Salmonella Enterica ◽  
Drug Targets ◽  
Protein Sequences ◽  
Analysis Approach ◽  
Essential Proteins ◽  
Pathways Analysis

Objective: In the present study, an attempt has been made for subtractive proteomic analysis approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using computational tools. Method: Paralogous, redundant and less than 100 amino acid protein sequences were removed by using CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative Metabolic pathways analysis was performed to find unique and common metabolic pathways. The non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for drug targets while Psortb and CELLO were used to predict subcellular localization. Result: There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp. enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways. These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins showed druggability and can be used as a therapeutic target. Conclusion: Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic druggable proteins which are essential for the pathogen survival and non-homologous to human proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat against salmonellosis.

scholarly journals Screening of Potential Indonesia Herbal Compounds Based on Multi-Label Classification for 2019 Coronavirus Disease

2021 ◽  
Vol 5 (4) ◽  
pp. 75
Author(s):  
Aulia Fadli ◽  
Wisnu Ananta Kusuma ◽  
Annisa ◽  
Irmanida Batubara ◽  
Rudi Heryanto
Keyword(s):  
Drug Discovery ◽  
Drug Target ◽  
Deep Neural Network ◽  
Drug Repurposing ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Herbal Plants ◽  
Approved Drugs ◽  
Pubchem Fingerprint ◽  
F Measure

Coronavirus disease 2019 pandemic spreads rapidly and requires an acceleration in the process of drug discovery. Drug repurposing can help accelerate the drug discovery process by identifying new efficacy for approved drugs, and it is considered an efficient and economical approach. Research in drug repurposing can be done by observing the interactions of drug compounds with protein related to a disease (DTI), then predicting the new drug-target interactions. This study conducted multilabel DTI prediction using the stack autoencoder-deep neural network (SAE-DNN) algorithm. Compound features were extracted using PubChem fingerprint, daylight fingerprint, MACCS fingerprint, and circular fingerprint. The results showed that the SAE-DNN model was able to predict DTI in COVID-19 cases with good performance. The SAE-DNN model with a circular fingerprint dataset produced the best average metrics with an accuracy of 0.831, recall of 0.918, precision of 0.888, and F-measure of 0.89. Herbal compounds prediction results using the SAE-DNN model with the circular, daylight, and PubChem fingerprint dataset resulted in 92, 65, and 79 herbal compounds contained in herbal plants in Indonesia respectively.

scholarly journals Hunting for cures: Genomics and new diseasecontrol strategies

2003 ◽  
Vol 25 (6) ◽  
pp. 19-21
Author(s):  
Michael Ginger
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
New Drugs ◽  
Potential Drug ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Genomic Technologies ◽  
Potential Drug Targets

New drugs are needed urgently to win the war against parasites that cause many serious diseases that are endemic or resurgent in some of the World's poorest countries. Post-genomic technologies provide a powerful resource that can be exploited during the drug-discovery process. With genome sequencers able to uncover secrets from even the most experimentally intractable of pathogens, the complete and annotated genomes from a number of the most medically important parasites are now, or will soon be, published. Already, the information that has been released from these projects has been put to good use in identifying new potential drug targets.

scholarly journals Analysis of metabolic pathways in mycobacteria to aid drug-target identification

2019 ◽  
Author(s):  
Bridget P. Bannerman ◽  
Sundeep C. Vedithi ◽  
Jorge Júlvez ◽  
Pedro Torres ◽  
Vaishali P. Waman ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Causative Agent ◽  
Metabolic Pathways ◽  
Drug Target ◽  
Drug Targets ◽  
Opportunistic Infections ◽  
Target Identification ◽  
Treatment Strategies ◽  
New Drugs ◽  
Drug Target Identification

AbstractThree related mycobacteria are the cause of widespread infections in man and are the focus of intense research and drug-discovery efforts in the face of growing antimicrobial resistance.Mycobacterium tuberculosis, the causative agent of tuberculosis, is currently one of the top ten causes of death in the world according to WHO;M.abscessus, a group of non-tuberculous mycobacteria causes lung infections and other opportunistic infections in humans; andM.leprae, the causative agent of leprosy, remains endemic in tropical countries. There is an urgent need to design alternatives to conventional treatment strategies, due to the increase in resistance to standard antibacterials. In this study, we present a comparative analysis of chokepoint and essentiality datasets that will provide insight into the development of new treatment regimes. We illustrate the key metabolic pathways shared between these three organisms and identify drug targets with a wide metabolic impact that are common to the three species. We demonstrate that 72% of the chokepoint enzymes are proteins essential toMycobacterium tuberculosis. We show also that 78% of the drug targets, prioritized based on their presence in multiple paths on the metabolic network, are present in pathways shared byM. tuberculosis, M.lepraeandM.abscessus, including biosynthesis of amino acids, carbohydrates, cell structures, fatty acid and lipid biosynthesis. A further 17% is found in the prioritised pathways shared betweenM. tuberculosisandM.abscessus. We have performed comparative structure modelling of potential drug targets identified using our analysis in order to assess druggability and demonstrate the importance of chokepoint analysis in terms of drug target identification.AUTHOR SUMMARYComputer simulation studies to design new drugs against mycobacteria

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