scholarly journals Anthraquinone derivatives as an immune booster and their therapeutic option against COVID-19

2020 ◽  
Author(s):  
Pukar Khanal ◽  
BM Patil ◽  
Jagdish chand ◽  
Yasmin Naaz
Keyword(s):  
Binding Affinity ◽  
Kegg Pathway ◽  
Therapeutic Option ◽  
Docking Study ◽  
Spike Protein ◽  
Pathway Database ◽  
Kegg Pathway Database ◽  
Anthraquinone Derivatives ◽  
Novel Coronavirus ◽  
Immune Booster

Abstract Multiple Anthraquinolines derivatives are reported for their immune-boosting, anti-inflammatory and anti-viral efficacy. Hence, the present study dealt to investigate the reported anthraquinone derivatives as an immune booster molecule in COVID-19 infection and evaluate their binding affinity with three reported targets of novel coronavirus i.e. 3CLpro, PLpro and spike proteins. The reported anthraquinone derivatives were retrieved from an open-source database and filtered based on a positive druglikeness score. Further, the probably modulated gene by compounds with positive druglikeness score was evaluated for the modulation of proteins using DIGEP-Pred and the interaction of proteins was evaluated using STRING; associated pathways were recorded concerning the KEGG pathway database. Finally, docking was carried using autodock4; pose scoring minimum binding energy was chosen to visualize the ligand-protein interaction. Among 101 compounds, 36 scored positive druglikeness scores; modulating multiple pathways for immune-boosting as well as pathways involved in infectious and non-infectious diseases. Similarly, docking study revealed torososide B to have the highest binding affinity with PLpro and 3clpro and 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone-3-O-(6'-O-acetyl)-β-D-xylopyranosyl-(1->2)-β-D-glucopyranoside with spike protein

scholarly journals Anthraquinone Derivatives as an Immune Booster and their Therapeutic Option Against COVID-19

2020 ◽  
Vol 10 (5) ◽  
pp. 325-335 ◽  
Author(s):  
Pukar Khanal ◽  
B. M. Patil ◽  
Jagdish Chand ◽  
Yasmin Naaz
Keyword(s):  
Binding Energy ◽  
Binding Affinity ◽  
Immune Modulation ◽  
Therapeutic Option ◽  
Docking Study ◽  
Spike Protein ◽  
Pathway Database ◽  
Anthraquinone Derivatives ◽  
Novel Coronavirus ◽  
Immune Booster

Abstract Anthraquinone derivatives are identified for their immune-boosting, anti-inflammatory, and anti-viral efficacy. Hence, the present study aimed to investigate the reported anthraquinone derivatives as immune booster molecules in COVID-19 infection and evaluate their binding affinity with three reported targets of novel coronavirus i.e. 3C-like protease, papain-like protease, and spike protein. The reported anthraquinone derivatives were retrieved from an open-source database and filtered based on a positive druglikeness score. Compounds with positive druglikeness scores were predicted for their targets using DIGEP-Pred and the interaction among modulated proteins was evaluated using STRING. Further, the associated pathways were recorded concerning the Kyoto Encyclopedia of Genes and Genomes pathway database. Finally, the docking was performed using autodock4 to identify the binding efficacy of anthraquinone derivatives with 3C-like protease, papain-like protease, and spike protein. After docking the pose of ligand scoring minimum binding energy was chosen to visualize the ligand–protein interaction. Among 101 bioactives, 36 scored positive druglikeness score and regulated multiple pathways concerned with immune modulation and (non-) infectious diseases. Similarly, docking study revealed torososide B to possess the highest binding affinity with papain-like protease and 3C-like protease and 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone-3-O-(6′-O-acetyl)-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside with spike protein. Graphic Abstract

scholarly journals Computational approach for the design of potential spike protein binding natural compounds in SARS- CoV2

2020 ◽  
Author(s):  
Anamika Basu ◽  
Anasua Sarkar ◽  
Ujjwal Maulik
Keyword(s):  
Natural Products ◽  
Protein Binding ◽  
Binding Site ◽  
Transmembrane Protein ◽  
Experimental Studies ◽  
Cost Effective ◽  
Docking Study ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Novel Coronavirus

Abstract Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role as it is rapid, cost effective, compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus effected patients, in the present alarming situation. In this paper five phytochemicals which belong to flavonoid and anthraquinone subclass, selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. From the detail analysis of their molecular binding site on spike protein binding site with its receptor, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19.

scholarly journals Meta-Analysis of Differential miRNA Expression after Bariatric Surgery

2019 ◽  
Vol 8 (8) ◽  
pp. 1220 ◽  
Author(s):  
Gladys Langi ◽  
Lukasz Szczerbinski ◽  
Adam Kretowski
Keyword(s):  
Bariatric Surgery ◽  
Target Genes ◽  
Web Of Science ◽  
Kegg Pathway ◽  
Meta Analysis ◽  
Obese Patients ◽  
Pathway Database ◽  
Efficient Treatment ◽  
Kegg Pathway Database ◽  
Before And After

Bariatric surgery is an efficient treatment for weight loss in obese patients and for resolving obesity comorbidities. However, the mechanisms behind these outcomes are unclear. Recent studies have indicated significant alterations in the transcriptome after surgery, specifically in the differential expression of microRNAs. In order to summarize the recent findings, we conducted a systematic summary of studies comparing microRNA expression levels before and after surgery. We identified 17 animal model and human studies from four databases (Ovid, Scopus, Web of Science, and PubMed) to be enrolled in this meta-analysis. From these studies, we identified 14 miRNAs which had the same direction of modulation of their expression after surgery in at least two studies (downregulated: hsa-miR-93-5p, hsa-miR-106b-5p, hsa-let-7b-5p, hsa-let-7i-5p, hsa-miR-16-5p, hsa-miR-19b-3p, hsa-miR-92a-3p, hsa-miR-222-3p, hsa-miR-142-3p, hsa-miR-140-5p, hsa-miR-155-5p, rno-miR-320-3p; upregulated: hsa-miR-7-5p, hsa-miR-320c). Pathway analysis for these miRNAs was done using database resources (DIANA-TarBase and KEGG pathway database) and their predicted target genes were discussed in relation with obesity and its comorbidities. Discrepancies in study design, such as miRNA source, bariatric surgery type, time of observation after surgery, and miRNA profiling methods, were also discussed.

Chemogenomic analysis of neuronal differentiation with pathway changes in PC12 cells

2016 ◽  
Vol 12 (1) ◽  
pp. 283-294 ◽  
Author(s):  
Jack Yu-Shih Lin ◽  
Chien Liang Wu ◽  
Chia Nan Liao ◽  
Akon Higuchi ◽  
Qing-Dong Ling
Keyword(s):  
Molecular Biology ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Kegg Pathway ◽  
Chemical Elements ◽  
Pathway Database ◽  
Kegg Pathway Database

The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database creates networks from interrelations between molecular biology and underlying chemical elements.

scholarly journals In silico screening of JAK-STAT modulators from the antiviral plants of Indian traditional system of medicine with the potential to inhibit 2019 novel coronavirus

2020 ◽  
Author(s):  
Pukar Khanal ◽  
Taaza Duyu ◽  
BM Patil ◽  
Yadu Nandan Dey ◽  
Ismail Pasha ◽  
...  
Keyword(s):  
Immune System ◽  
Hepatitis Virus ◽  
Docking Study ◽  
Spike Protein ◽  
Murine Hepatitis Virus ◽  
Traditional System ◽  
Diarrhea Virus ◽  
Associated Proteins ◽  
Novel Coronavirus ◽  
Stat Pathway

Abstract Aim. The present study was aimed to identify the lead hits from reported anti-viral Indian medicinal plants to modulate the proteins through the JAK-STAT pathway and to identify the proteins that share the domain with coronavirus (COVID19) associated proteins i.e. 3CLpro, PLpro, and spike protein. Methods. The reported anti-viral plants were screened from the available databases and published literature; their phytoconstituents were retrieved, gene-expression was predicted and the modulated proteins in JAK-STAT pathway were predicted. The interaction between proteins was evaluated using STRING and the network between phytoconstituents and proteins was constructed using Cytoscape. The druglikeness score was predicted using MolSoft and the ADMET profile of phytoconstituents was evaluated using admetSAR2.0. The domain of three proteins i.e. 3CLpro, PLpro, and spike protein of coronavirus was compared using NCBI blastP against the RCSB database. Results. The majority of the phytoconstituents from the anti-viral plants were predicted to target TRAF5 protein in the JAK-STAT pathway; among them, vitexilactone was predicted to possess the highest druglikeness score. Proteins targeted in the JAK-STAT pathways were also predicted to modulate the immune system. Similarly, the docking study identified sesaminol 2-O-β-D-gentiobioside to possess the highest binding affinity with spike protein. Similarly, phylogeny comparison also identified the common protein domains with other stains of microbes like murine hepatitis virus strain A59, avian infectious bronchitis virus, and porcine epidemic diarrhea virus CV777. Conclusion. Although, the present study is based on computer simulations and database mining, it provides two important aspects in identifying the lead hits against coronavirus. First, targeting the JAK-STAT pathway in the corona-infected host by folk anti-viral agents can regulate the immune system which would inhibit spreading the virus inside the subject. Secondly, the well-known targets of coronavirus i.e. 3CLpro, PLpro, and spike protein share some common domains with other proteins of different microbial strains.

scholarly journals V367F mutation in SARS-CoV-2 spike RBD emerging during the early transmission phase enhances viral infectivity through increased human ACE2 receptor binding affinity

2021 ◽  
Author(s):  
Junxian Ou ◽  
Zhonghua Zhou ◽  
Ruixue Dai ◽  
Jing Zhang ◽  
Shan Zhao ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Receptor Binding ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Critical Determinant ◽  
Evolutionary Trajectory ◽  
Receptor Binding Affinity ◽  
Protein Receptor ◽  
Novel Coronavirus ◽  
Transmission Phase

The current pandemic of COVID-19 is caused by a novel coronavirus SARS-CoV-2. The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, firstly we analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human ACE2 receptor. Among 32,123 genomes of SARS-CoV-2 isolates (January through March, 2020), 302 non-synonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding ELISA, surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F + D614G) which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. Importance A novel coronavirus SARS-CoV-2 has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether the mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious, has been the research hotspot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human ACE2 receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.

scholarly journals KEGGtranslator: visualizing and converting the KEGG PATHWAY database to various formats

2011 ◽  
Vol 27 (16) ◽  
pp. 2314-2315 ◽  
Author(s):  
Clemens Wrzodek ◽  
Andreas Dräger ◽  
Andreas Zell
Keyword(s):  
Kegg Pathway ◽  
Pathway Database ◽  
Kegg Pathway Database

scholarly journals Withanolides from Withania somnifera as an immune booster and their therapeutic option against COVID-19

2020 ◽  
Author(s):  
Pukar Khanal ◽  
B. M. Patil ◽  
Ismail Pasha ◽  
Yadu Nandan Dey ◽  
Sharad Chand
Keyword(s):  
Immune System ◽  
Withania Somnifera ◽  
Fluid Shear Stress ◽  
Therapeutic Option ◽  
Spike Protein ◽  
Fluid Shear ◽  
Protein Protein Interaction ◽  
Hydrogen Bond Interactions ◽  
Network Interaction ◽  
Immune Booster

Abstract Aim: The present study aimed to investigate the withanolides as an immune system booster and anti-viral agents against the coronavirus.Materials and Methods: Reported withanolides from Withinana somnifera were retrieved from the open-source database i.e. ChEBI, PCIDB and Dr. Duke's Phytochemical and Ethnobotanical Databases. Their protein-based targets were predicted using DigepPred and the protein-protein interaction was evaluated using STRING. Similarly, the drug-likeness score of individual compounds was predicted using MolSoft and intestinal absorptivity was predicted using the boiled-egg model. The network among the compounds, proteins, and modulated pathways was constructed using Cytoscape and the docking was performed using autodock4.0.Results: Withanoloid Q was predicted to modulate the highest number of proteins, showed positive human intestinal absorption and had the highest druglikeness score. Similarly, combined network interaction identified withanolide Q to target the highest number of proteins; RAC1 was majorly modulated and regulating Fluid shear stress and atherosclerosis as a majorly regulated pathway. Similarly, Withanolide D and Withanolide G were predicted to have the better binding affinity with PLpro, Withanolide M with 3clpro, and Withanolide M with spike protein based on binding energy and number of hydrogen bond interactions. Conclusion: Among the multiple withanolides from Withania somnifera, withanolide-D, -G, -M, and -Q were predicted as a lead hit based on druglikeness score, modulated proteins, and docking score to boost immune system and inhibit the COVID infection.

scholarly journals TbasCO: Trait-based Comparative ’Omics Identifies Ecosystem-Level and Niche- Differentiating Adaptations of an Engineered Microbiome

2021 ◽  
Author(s):  
E.A. McDaniel ◽  
J.J.M van Steenbrugge ◽  
D.R. Noguera ◽  
K.D. McMahon ◽  
J.M. Raaijmakers ◽  
...  
Keyword(s):  
Kegg Pathway ◽  
Marker Genes ◽  
Grand Challenge ◽  
Biological Phosphorus Removal ◽  
Pathway Database ◽  
Kegg Pathway Database ◽  
Metabolic Versatility ◽  
Transcriptional Pattern ◽  
Ecosystem Level ◽  
Biological Phosphorus

ABSTRACTA grand challenge in microbial ecology is disentangling the traits of individual populations within complex communities. Various cultivation-independent approaches have been used to infer traits based on the presence of marker genes. However, marker genes are not linked to traits with complete fidelity, nor do they capture important attributes, such as the timing of expression or coordination among traits. To address this, we present an approach for assessing the trait landscape of microbial communities by statistically defining a trait attribute as shared transcriptional pattern across multiple organisms. Leveraging the KEGG pathway database as a trait library and the Enhanced Biological Phosphorus Removal (EBPR) model microbial ecosystem, we demonstrate that a majority (65%) of traits present in 10 or more genomes have niche-differentiating expression attributes. For example, while 14 genomes containing the high-affinity phosphorus transporter pstABCS display a canonical attribute (e.g. up-regulation under phosphorus starvation), we identified another attribute shared by 11 genomes where transcription was highest under high phosphorus conditions. Taken together, we provide a novel framework for revealing hidden metabolic versatility when investigating genomic data alone by assigning trait-attributes through genome-resolved time-series metatranscriptomics.

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