In silico identification of novel IL-1β inhibitors to target protein–protein interfaces

Halim, Sobia Ahsan; Jawad, Muhammad; Ilyas, Muhammad; Mir, Zulfiqar Ali; Mirza, Atif Anwar; Husnain, Tayyab

doi:10.1016/j.compbiolchem.2015.06.004

Cited by 15 publications

(7 citation statements)

References 32 publications

(33 reference statements)

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“…9 ) revealed the interaction of the ketonic oxygen with the side chain amino group of Lys63. In addition, the phenolic group in ring A mediated hydrogen bond interaction with the side chain amino group of Lys132 [ 43 ]. C-ring of compound 2 was stabilized by hydrophobic interactions provided by the side chains of the surrounding residues.…”

Section: Resultsmentioning

confidence: 99%

Bio-guided isolation of potential anti-inflammatory constituents of some endophytes isolated from the leaves of ground cherry (Physalis pruinosa L.) via ex-vivo and in-silico studies

Mahana

Hammoda

Saad

et al. 2023

BMC Complement Med Ther

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Background Due to the extensive potential of previously studied endophytes in addition to plants belonging to genus Physalis as a source of anti-inflammatory constituents, the present study aimed at isolation for the first time some endophytic fungi from the medicinal plant Physalis pruinosa. Methods The endophytic fungi were isolated from the fresh leaves of P. pruinosa then purified and identified by both morphological and molecular methods. Comparative evaluation of the cytotoxic and ex vivo anti-inflammatory activity in addition to gene expression of the three pro-inflammatory indicators (TNF-α, IL-1β and INF-γ) was performed in WBCs treated with lipopolysaccharide (LPS) for the identified endophytes, isolated compounds and the standard anti-inflammatory drug (piroxicam). For prediction of the binding mode of the top-scoring constituents-targets complexes, the Schrödinger Maestro 11.8 package (LLC, New York, NY) was employed in the docking study. Results A total of 50 endophytic fungal isolates were separated from P. pruinosa leaves. Selection of six representative isolates was performed for further bioactivity screening based on their morphological characters, which were then identified as Stemphylium simmonsii MN401378, Stemphylium sp. MT084051, Alternaria infectoria MT573465, Alternaria alternata MZ066724, Alternaria alternata MN615420 and Fusarium equiseti MK968015. It could be observed that A. alternata MN615420 extract was the most potent anti-inflammatory candidate with a significant downregulation of TNF-α. Moreover, six secondary metabolites, alternariol monomethyl ether (1), 3’-hydroxyalternariol monomethyl ether (2), alternariol (3), α-acetylorcinol (4), tenuazonic acid (5) and allo-tenuazonic acid (6) were isolated from the most potent candidate (A. alternata MN615420). Among the tested isolated compounds, 3’-hydroxyalternariol monomethyl ether showed the highest anti-inflammatory potential with the most considerable reductions in the level of INF-γ and IL-1β. Meanwhile, alternariol monomethyl ether was the most potent TNF-α inhibitor. The energy values for the protein (IL-1β, TNF-α and INF-γ)–ligand interaction for the best conformation of the isolated compounds were estimated using molecular docking analysis. Conclusions The results obtained suggested alternariol derivatives may serve as naturally occurring potent anti-inflammatory candidates. This study opens new avenues for the design and development of innovative anti-inflammatory drugs that specifically target INF-γ, IL-1β and INF-γ.

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Section: Resultsmentioning

confidence: 99%

Bio-guided isolation of potential anti-inflammatory constituents of some endophytes isolated from the leaves of ground cherry (Physalis pruinosa L.) via ex-vivo and in-silico studies

Mahana

Hammoda

Saad

et al. 2023

BMC Complement Med Ther

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“…These interaction sites play a significant role in receptor binding and signal induction. As a result, they might serve as targeted locations for compound binding, and the residues were identified for the active site for molecular docking analysis [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Assessment of Antioxidant, Immunomodulatory Activity of Oxidised Epigallocatechin-3-Gallate (Green Tea Polyphenol) and Its Action on the Main Protease of SARS-CoV-2—An In Vitro and In Silico Approach

et al. 2022

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Owing to the instability of Epigallocatechin Gallate (EGCG), it may undergo auto-oxidation and form oxidised products or dimers. In the present study, we aimed to evaluate the therapeutic effects, including antioxidation and immunomodulatory action, of the Oxidised Epigallocatechin Gallate (O-EGCG) as compared to native EGCG and the action of these compounds on main protease (Mpro) docking against SARS-CoV-2. HCT-116 (Human Colon Cancer) cell lines were used to estimate the total antioxidant capacity and lipid peroxidation levels and pro-inflammatory markers (human IL-6, IL-1β, TNF-α). Further, molecular docking analysis was performed by AutoDock and visualised in Discovery studio. Improved antioxidant capacity of O-EGCG was observed, and there was a significant decrease in the inflammatory markers (IL-1β, IL-6, and TNF-α) when O-EGCG was applied as compared to EGCG. The O-EGCG was shown to be strongly associated with the highest docking score and active site residues of IL-1, IL-6, and TNF- α, as well as the Mpro of SARS-CoV-2, according to in silico approach. The in vitro and in silico analyses indicate an improved therapeutic action of the oxidised form of EGCG. The effective inhibitory action of O-EGCG against SARS-CoV-2 suggests further exploration of the compound against COVID-19 and its efficacy. However, in vivo studies and understanding of the mechanism of action of O-EGCG may yield a better opinion on the use of O-EGCG and future human clinical trials.

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“…Successful docking studies have been performed in the recent years (Zaheer-ul-Haq et al, 2010 ; Halim et al, 2015 ). Recently several novel immunomodulators were designed using in silico approaches when screened against Interleukin-2 (Halim et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Both structure and ligand based methods are used to predict binding affinities of newly designed compounds. With our interest in computational analysis of several biologically important drug targets (Halim et al, 2013 , 2015 ; Halim and Zaheer-ul-Haq, 2015 ), we conducted this study to identify novel and effective DENV NS3-helicase inhibitors in silico . The compound which shows potential will be selected for biological testing in future to accelerate the therapeutic process against dengue.…”

Section: Introductionmentioning

confidence: 99%

Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

Halim

Khan

et al. 2017

Front. Chem.

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Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, 25 compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

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In silico identification of novel IL-1β inhibitors to target protein–protein interfaces

Cited by 15 publications

References 32 publications

Bio-guided isolation of potential anti-inflammatory constituents of some endophytes isolated from the leaves of ground cherry (Physalis pruinosa L.) via ex-vivo and in-silico studies

Bio-guided isolation of potential anti-inflammatory constituents of some endophytes isolated from the leaves of ground cherry (Physalis pruinosa L.) via ex-vivo and in-silico studies

Assessment of Antioxidant, Immunomodulatory Activity of Oxidised Epigallocatechin-3-Gallate (Green Tea Polyphenol) and Its Action on the Main Protease of SARS-CoV-2—An In Vitro and In Silico Approach

Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

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