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Journal ArticleDOI

Targeting IL-17 AND IL-17D receptors of rheumatoid arthritis using phytocompounds: A Molecular Docking study

01 Nov 2017-Vol. 263, Iss: 2, pp 022040
TL;DR: Light is shed on the anti-inflammatory mechanism of phytocompounds by targeting IL-17 and IL-D for effective treatment of RA through in silico investigations using Patch Dock algorithm.
Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune condition of the connective tissue in synovial joints, characterized by inflammation which can lead to bone and cartilage destruction. IL-17 and IL-17D cytokines produced by a number of cell types, primarily promote pro-inflammatory immune responses and negative regulator in fibroblast growth factor signalling. Thus, the promising therapeutic strategies focus on targeting these cytokines, which has led to the identification of effective inhibitors. However, several studies focused on identifying the anti-arthritic potential of natural compounds. Therefore, in the present study we undertook in silico investigations to decipher the anti-inflammatory prospective of phytocompounds by targeting IL-17 and IL-17D cytokines using Patch Dock algorithm. Additionally, IL-17 and IL-17D proteins structure were modelled and validated for molecular docking study. Further, phytocompounds based on anti-inflammatory property were subjected to Lipinski filter and ADMET properties indicated that all of these compounds showed desirable drug-like criteria. The outcome of this investigation sheds light on the anti-inflammatory mechanism of phytocompounds by targeting IL-17 and IL-D for effective treatment of RA.
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Journal Article
TL;DR: This in silico study suggests that these investigated polyphenols could serve as better replacements for synthetic drugs such as allopurinol in the management of gouty arthritis.
Abstract: The binding of Interleukin-17A (IL-17A) to its receptor causes the release of chemokine which have an implication in the pathogenesis of gouty arthritis. Though, some synthetic drugs have been proved worthy as IL-17A inhibitors in the management of gout but they have been associated with a number of side effects. Polyphenols have been documented for numerous therapeutic applications. In spite of this, there are scarce data on the mechanism of action and protective potentials of polyphenolic against gouty arthritis. This present in silico study aimed to assess the inhibitory potentials and ADMET properties of selected polyphenols against IL-17A using molecular docking tools. The crystal structure of IL-17A was retrieved from the protein database, while the structures of polyphenolic compounds were retrieved from Pubchem. Drug-likeness of the polyphenols was assessed using DruLiTo. A total of 22 out of 26 polyphenols investigated passed the Lipinski drug likeness rule of five which were then docked with the active site of IL-17A using docking software, and the docked complexes were analyzed using LigPlot and protein-ligand profiler web server. The results showed that all the investigated polyphenols have appreciable higher binding affinity when compared to the standard drug (allopurinol) with pelargondin and catechin having the highest binding affinity (-7.5 kcal/mol). Furthermore, ADMET screening were carried out on the five compounds with the best hits. Conclusively, this in silico study suggests that these investigated polyphenols could serve as better replacements for synthetic drugs such as allopurinol in the management of gouty arthritis. DOI: http://dx.doi.org/10.5281/zenodo.4064236

Cites background from "Targeting IL-17 AND IL-17D receptor..."

  • ...arthritis [11, 22, 25] and available synthetic drugs are accompanied with a number of side effects alongside their therapeutic efficacies [1, 39]....

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  • ...Though, synthetic drugs such as allopurinol are effective in the management of gouty arthritis which may be due to their ability to target and inhibit IL-17A, however, they are usually accompanied with several complications such as gastrointestinal distress, hypersensitivity reactions, skin rash, elevated blood glucose and pressure, diarrhea, and vomiting in patients [1, 37-39]....

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References
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Journal ArticleDOI
TL;DR: The PROCHECK suite of programs as mentioned in this paper provides a detailed check on the stereochemistry of a protein structure and provides an assessment of the overall quality of the structure as compared with well refined structures of the same resolution.
Abstract: The PROCHECK suite of programs provides a detailed check on the stereochemistry of a protein structure Its outputs comprise a number of plots in PostScript format and a comprehensive residue-by-residue listing These give an assessment of the overall quality of the structure as compared with well refined structures of the same resolution and also highlight regions that may need further investigation The PROCHECK programs are useful for assessing the quality not only of protein structures in the process of being solved but also of existing structures and of those being modelled on known structures

22,829 citations


"Targeting IL-17 AND IL-17D receptor..." refers methods in this paper

  • ...Validations of the modeled proteins were carried out with PROCHECK using Ramachandran plot [17]....

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Journal ArticleDOI
TL;DR: The new SwissADME web tool is presented that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar are presented.
Abstract: To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

6,135 citations


"Targeting IL-17 AND IL-17D receptor..." refers methods in this paper

  • ...The most important phytochemical property Lipinski rule of five predicted using SWISSADME on-line server [18]....

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Journal ArticleDOI
TL;DR: The iterative threading assembly refinement (I-TASSER) server is an integrated platform for automated protein structure and function prediction based on the sequence- to-structure-to-function paradigm.
Abstract: The iterative threading assembly refinement (I-TASSER) server is an integrated platform for automated protein structure and function prediction based on the sequence-to-structure-to-function paradigm. Starting from an amino acid sequence, I-TASSER first generates three-dimensional (3D) atomic models from multiple threading alignments and iterative structural assembly simulations. The function of the protein is then inferred by structurally matching the 3D models with other known proteins. The output from a typical server run contains full-length secondary and tertiary structure predictions, and functional annotations on ligand-binding sites, Enzyme Commission numbers and Gene Ontology terms. An estimate of accuracy of the predictions is provided based on the confidence score of the modeling. This protocol provides new insights and guidelines for designing of online server systems for the state-of-the-art protein structure and function predictions. The server is available at http://zhanglab.ccmb.med.umich.edu/I-TASSER.

5,792 citations


"Targeting IL-17 AND IL-17D receptor..." refers methods in this paper

  • ...Lack of full length template protein we were generated IL-17 and IL-17D protein structure using abinitio modelling with I-TASSER (Iterative Threading Assembly Refinement) on-line server by iterative structural fragment reassembly [16]....

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Journal ArticleDOI
TL;DR: Two freely available web servers for molecular docking that perform structure prediction of protein–protein and protein–small molecule complexes and the SymmDock method predicts the structure of a homomultimer with cyclic symmetry given theructure of the monomeric unit are described.
Abstract: Here, we describe two freely available web servers for molecular docking. The PatchDock method performs structure prediction of protein-protein and protein-small molecule complexes. The SymmDock method predicts the structure of a homomultimer with cyclic symmetry given the structure of the monomeric unit. The inputs to the servers are either protein PDB codes or uploaded protein structures. The services are available at http://bioinfo3d.cs.tau.ac.il. The methods behind the servers are very efficient, allowing large-scale docking experiments.

2,590 citations


"Targeting IL-17 AND IL-17D receptor..." refers methods in this paper

  • ...Molecular docking Molecular docking analysis was performed using the geometry-based PatchDock algorithm [19]....

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Journal ArticleDOI
TL;DR: The 2012 ACR RA recommendations were developed by two expert panels: a non-voting working group and Core Expert Panel of clinicians and methodologists responsible for the selection of the relevant topic areas to be considered, the systematic literature review, and the evidence synthesis.
Abstract: The American College of Rheumatology (ACR) most recently published recommendations for use of disease modifying anti-rheumatic drugs (DMARDs) and biologics in the treatment of rheumatoid arthritis (RA) in 2008 (1). These recommendations covered indications for use, monitoring of side-effects, assessment of the clinical response to DMARDs and biologics, screening for tuberculosis (TB), and assessment of the roles of cost and patient preference in decision-making for biologic agents (1). Recognizing the rapidly evolving knowledge in RA management and the accumulation of new evidence regarding the safety and efficacy of existing and newer therapies, the ACR commissioned an update of the 2008 recommendations in select topic areas. The 2012 revision updates the 2008 ACR recommendations in the following areas: (1) indications for DMARDs and biologics; (2) switching between DMARD and biologic therapies; (3) use of biologics in high-risk patients (those with hepatitis, congestive heart failure, and malignancy); (4) screening for TB in patients starting or currently receiving biologics; and (5) vaccination in patients starting or currently receiving DMARDs or biologics (Table 1). Table 1 Overview Comparison of Topics and Medications Included in the 2008 and 2012 ACR RA Recommendations METHODS We utilized the same methodology as described in detail in the 2008 guidelines (1) to maintain consistency and to allow cumulative evidence to inform this 2012 recommendation update. These recommendations were developed by two expert panels: (1) a non-voting working group and Core Expert Panel (CEP) of clinicians and methodologists responsible for the selection of the relevant topic areas to be considered, the systematic literature review, and the evidence synthesis and creation of “clinical scenarios”; and (2) a Task Force Panel (TFP) of 11 internationally-recognized expert clinicians, patient representatives and methodologists with expertise in RA treatment, evidence-based medicine and patient preferences who were tasked with rating the scenarios created using an ordinal scale specified in the Research and Development/University of California at Los Angeles (RAND/UCLA) Appropriateness method (2–4). This method solicited formal input from a multi-disciplinary TFP panel to make recommendations informed by the evidence. The methods used to develop the updated ACR recommendations are described briefly below. Systematic Literature Review – Sources, Databases and Domains Literature searches for both DMARDs and biologics relied predominantly on PubMed searches) with medical subject headings (MeSH) and relevant keywords similar to those used for the 2008 ACR RA recommendations (see Appendices 1 and 2). We included randomized clinical trials (RCTs), controlled clinical trials (CCTs), quasi-experimental designs, cohort studies (prospective or retrospective), and case-control studies, with no restrictions on sample size. More details about inclusion criteria are listed below and in Appendix 3. The 2008 recommendations were based on a literature search that ended on February 14, 2007. The literature search end date for the 2012 Update was February 26, 2010 for the efficacy and safety studies and September 22, 2010 for additional qualitative reviews related to TB screening, immunization and hepatitis (similar to the 2008 methodology). Studies published subsequent to that date were not included. For biologics, we also reviewed the Cochrane systematic reviews and overviews (published and in press) in the Cochrane Database of Systematic Reviews to identify additional studies (5–8) and further supplemented by hand-checking the bibliographies of all included articles. Finally, the CEP and TFP confirmed that relevant literature was included for evidence synthesis. Unless they were identified by the literature search and met the article inclusion criteria (see Appendix 3), we did not review any unpublished data from product manufacturers, investigators, or the Food and Drug Administration (FDA) Adverse Event Reporting System. We searched the literature for the eight DMARDs and nine biologics most commonly used for the treatment of RA. Literature was searched for eight DMARDS including azathioprine, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, minocycline, organic gold compounds and sulfasalazine. As in 2008, azathioprine, cyclosporine and gold were not included in the recommendations based on infrequent use and lack of new data (Table 1). Literature was searched for nine biologics including abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab; anakinra was not included in the recommendations due to infrequent use and lack of new data. Details of the bibliographic search strategy are listed in Appendix 1.

1,493 citations