Computational Overview of Mycobacterial Thymidine Monophosphate Kinase

2020 ◽  
Vol 26 (15) ◽  
pp. 1676-1681
Author(s):  
Sana Gul ◽  
Ruqaiya Khalil ◽  
Zaheer Ul-Haq ◽  
Mohammad S. Mubarak
Keyword(s):  
Molecular Docking ◽  
Structure Elucidation ◽  
Tuberculosis Patient ◽  
Review Article ◽  
Morbidity Rate ◽  
Drug Resistant ◽  
Tuberculosis Control ◽  
Bacterial Enzyme ◽  
High Prevalence ◽  
Thymidine Monophosphate

: Tuberculosis (TB) ranks among the diseases with the highest morbidity rate with significantly high prevalence in developing countries. Globally, tuberculosis poses the most substantial burden of mortality. Further, a partially treated tuberculosis patient is worse than untreated; they may lead to standing out as a critical obstacle to global tuberculosis control. The emergence of multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains, and co-infection of HIV further worsen the situation. The present review article discusses validated targets of the bacterial enzyme thymidine monophosphate kinase (TMPK). TMPKMTB enzyme belongs to the nucleoside monophosphate kinases (NMPKs) family. It is involved in phosphorylation of TMP to TDP, and TDP is phosphorylated to TTP. This review highlights structure elucidation of TMP enzymes and their inhibitors study on TMP scaffold, and it also discusses different techniques; including molecular docking, virtual screening, 3DPharmacophore, QSAR for finding anti-tubercular agents.

scholarly journals In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Padikkamannil Abishad ◽  
Pollumahanti Niveditha ◽  
Varsha Unni ◽  
Jess Vergis ◽  
Nitin Vasantrao Kurkure ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Antimicrobial Efficacy ◽  
Drug Resistant ◽  
Protein Motifs ◽  
Phytochemical Compounds ◽  
In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

scholarly journals Anti-Infective and Antiviral Activity of Valinomycin and Its Analogues from a Sea Cucumber-Associated Bacterium, Streptomyces sp. SV 21

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 81
Author(s):  
Joko T. Wibowo ◽  
Matthias Y. Kellermann ◽  
Matthias Köck ◽  
Masteria Y. Putra ◽  
Tutik Murniasih ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Structure Elucidation ◽  
Nmr Spectra ◽  
Sea Cucumber ◽  
Spectroscopic Techniques ◽  
Drug Resistant ◽  
Molecular Fragments ◽  
1H And 13C Nmr ◽  
Positive Strain ◽  
Infective Potential

The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (3), streptodepsipeptide P11A (2), streptodepsipeptide P11B (1), and one novel valinomycin analogue, streptodepsipeptide SV21 (4), which were all produced by the Gram-positive strain Streptomycescavourensis SV 21. Although the exact molecular weight and major molecular fragments were recently reported for compound 4, its structure elucidation was not based on compound isolation and spectroscopic techniques. We successfully isolated and elucidated the structure based on the MS2 fragmentation pathways as well as 1H and 13C NMR spectra and found that the previously reported structure of compound 4 differs from our analysis. Our findings showed the importance of isolation and structure elucidation of bacterial compounds in the era of fast omics technologies. The here performed anti-infective assays showed moderate to potent activity against fungi, multi drug resistant (MDR) bacteria and infectivity of the Hepatitis C Virus (HCV). While compounds 2, 3 and 4 revealed potent antiviral activity, the observed minor cytotoxicity needs further investigation. Furthermore, the here performed anti-infective assays disclosed that the symmetry of the valinomycin molecule is most important for its bioactivity, a fact that has not been reported so far.

Structure elucidation, DNA binding and molecular docking studies of natural compounds isolated from Crateva religiosa leaves

2021 ◽  
pp. 131976
Author(s):  
Mehtab Parveen ◽  
Afroz Aslam ◽  
Sharmin Siddiqui ◽  
Mohammad Tabish ◽  
Chullikkattil P. Pradeep ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Dna Binding ◽  
Structure Elucidation ◽  
Natural Compounds ◽  
Docking Studies ◽  
Molecular Docking Studies

scholarly journals The Biology and Role of Interleukin-32 in Tuberculosis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wu Li ◽  
Wanyan Deng ◽  
Jianping Xie
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Host Molecule ◽  
Tuberculosis Control ◽  
Promising Alternative ◽  
Extensively Drug Resistant ◽  
Important Host ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality globally, with nearly 10.4 million new cases of incidence and over 1.7 million deaths annually. Drug-resistant M. tuberculosis strains, especially multidrug-resistant or extensively drug-resistant strains, have further intensified the problem associated with tuberculosis control. Host-directed therapy is a promising alternative for tuberculosis control. IL-32 is increasingly recognized as an important host molecule against tuberculosis. In this review, we highlight the proinflammatory properties of IL-32 and the mode of action of IL-32 in mycobacterial infections to inspire the development of novel immunity-based countermeasures and host-directed therapies against tuberculosis.

scholarly journals Evaluation the Pulmonary Tuberculosis Control Program with Strategy DOTS in Puskesmas Tanah Kalikedinding Surabaya

2014 ◽  
Vol 2 (2) ◽  
pp. 251
Author(s):  
Adistha Eka Noveyani ◽  
Santi Martini
Keyword(s):  
Pulmonary Tuberculosis ◽  
Health Center ◽  
Control Program ◽  
Tuberculosis Patient ◽  
Tuberculosis Control ◽  
Control Programs ◽  
Department Of Health ◽  
Inhibiting Factor ◽  
Rate Evaluation ◽  
Almost All

ABSTRACTStrategy DOTS is the tuberculosis control programs. The program has implemented in Tanah Kalikedinding Health Center and has expected to reach CDR ≥ 70% and SR ≥ 85%, which closely related to the management of health centers. This study aimed to evaluate the implementation of the DOTS program in health center whose the results associated with indicators of tuberculosis. This was a descriptive design study with the population was all pulmonary specialist, tuberculosis officers and laboratory personnel and pulmonary tuberculosis patients. The number of Tuberculosis patient respondents was 32 respondents. Samples were chosen using purposive sampling. Data collected by interview questionnaire and checklist. The variables were the finding case, the TB treatment, the enabling factor and inhibiting factor, recording and reporting, and result of tuberculosis indicators. This study resulted that CDR in 2013 was 112% already reached the national target ≥ 70%. This success related to the finding case almost all patients > 2 weeks of cought and all (100%) patients were examinated sputum and diagnosed according to the steps of tuberculosis diagnosis in Indonesia Department of Health guidelines. While SR in 2013 was 65.5% did not reach the target ≥ 85%. It was caused of there are patients who did not have a taking drug observer (PMO). All (100%) patients ever forgot taking anti tuberculosis drugs. Change in schedule of visit to the continuation phase be 2×/month caused patients to forget taking anti tuberculosis drugs. The enabling factor was counseling routinely by health care workers in health center. Inhibiting factor was distance to health center by majority (65,5%) patients were > 1 km. So they needed vehicle to go to the health center. Recording and reporting using electronic systems and being reported by online. So it is expected all TB patients were expected have a taking drug observer and optimizing the role of the a taking drug observer to increase success rate.Keywords: DOTS strategy, Case Detection Rate, Success Rate, evaluation,                     Tuberculosis

scholarly journals Epidemiological situation on acute enteric infections in the Republic of Dagestan in 2011-2015

2016 ◽  
Vol 21 (5) ◽  
pp. 290-295
Author(s):  
Zarema G. Tagirova ◽  
D. R Akhmedov ◽  
N. M.-G Zulpukarova ◽  
Z. M Daniyalbecova
Keyword(s):  
Prevalence Rate ◽  
Morbidity Rate ◽  
Regional Feature ◽  
Epidemiological Features ◽  
Medical Institutions ◽  
Intestinal Infections ◽  
High Prevalence ◽  
Enteric Infections ◽  
The Republic ◽  
Epidemiological Situation

There were studied epidemiological features of the prevalence rate of acute intestinal infections (AII) in the Republic of Dagestan (RD). The prevalence rate of acute intestinal infections in RD was shown to correspond taken as a whole, to Russian indices, however, the regional feature is the high prevalence rate of shigellosis, there is remained a high proportion of the AII of unidentified etiology. There was substantiated the necessity of development and implementation of targeted programmes aimed at the decline in the morbidity rate in problematic territories. The solution to the problem of the AII in the Republic is possible only under the coordination of efforts of federal and local authorities, sanitary - epidemiological and medical institutions.

In silico Repurposing of Anticancer Drug (5-Fluorouracil) as an Antibacterial Agent against Klebsiella pneumoniae

2021 ◽  
Vol 18 ◽  
Author(s):  
Amey Sharma ◽  
Apoorva Rana ◽  
Lakshya Mangtani ◽  
Aakanksha Kalra ◽  
Ravi Ranjan Kumar Niraj
Keyword(s):  
Molecular Docking ◽  
Klebsiella Pneumoniae ◽  
Thymidylate Synthase ◽  
In Silico ◽  
Homology Modelling ◽  
Klebsiella Pneumonia ◽  
Drug Resistant ◽  
Vitro Analysis ◽  
In Vitro Analysis

Background: Infections caused by drug resistant microorganisms have been increasing worldwide thereby being one of the major causes of morbidity in the 21st century. Klebsiella pneumoniae is one such bacteria causing lung inflammation, lung injury and death. Emergence of hyper-virulent and drug resistant species such as ESBL and CRKP has made this microbe a serious and urgent threat. The pace of emergence of these species is outgrowing the development of novel drug and vaccine candidates thereby focusing on drug repurposing approach. Objective: 1. Homology Modelling of Thymidylate Synthase. 2. Verification of Modelled Structure. 3. Molecular Docking. 4. Molecular Dynamic Simulation of Docked Complex. 5. In vitro analysis of 5-FU activity against Klebsiella pneumonia. Method: The 3-D structure of Thymidylate Synthase was predicted using Swiss-Model server and validated by in silico approaches. - Determination protein-protein interactions using STRING database. - Molecular docking. - MD simulations of 5-FU with predicted structure of thymidylate synthase. - In vitro antimicrobial drug sensitivity assay at different concentrations. Result: Hydrogen bond was observed in Molecular Docking - Protein-ligand complex remains stable during simulation. - 5-FU shows antimicrobial activity against Klebsiella pneumonia during In vitro study. Conclusion: Both In silico as well as in vitro analysis have indicated that 5-FU can potentially be developed as an antimicrobial agent towards Klebsiella pneumonia

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