ArticlePloS one2022
Structure-based 3D-Pharmacophore modeling to discover novel interleukin 6 inhibitors: An in silico screening, molecular dynamics simulations and binding free energy calculations.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 49 citations in OpenAlex.
- Identification of Potential SARS-CoV-2 Main Protease (MPro) Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Approaches.International journal of molecular sciences · 2026Article
- Exploring potential phytocompounds from black cumin as drug molecules against SARS-CoV-2 infections through bioinformatics analysis.PloS one · 2026Article
- Multi-target drug discovery for rheumatoid arthritis: a comprehensive computational approach using bioactive compounds.Scientific reports · 2025Article
- Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6.Molecules (Basel, Switzerland) · 2025Article
- Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (Pf Grp94).Proteins · 2025Article
- Computational analysis of zoanthamine alkaloids from Zoanthus sp. as potential DKK1 and GSK-3β inhibitors for osteoporosis therapy via Wnt signaling.Scientific reports · 2025Article
- Immunomodulatory Potential of Kaempferol Isolated fromInternational journal of molecular sciences · 2025Article
- Molecular docking, pharmacological profiling, and MD simulations of glycolytic inhibitors targeting novel SARS CoV-2 main protease and spike protein.In silico pharmacology · 2025Article
- Computational Screening of IL-1 and IL-6 Inhibitors for Rheumatoid Arthritis: Insights from Molecular Docking and Dynamics Analysis.Current pharmaceutical design · 2025Article
- Biomarker integration and biosensor technologies enabling AI-driven insights into biological aging.Frontiers in aging · 2025Review
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- Regulatory Role of IL6 in Immune-Related Adverse Events during Checkpoint Inhibitor Treatment in Melanoma.International journal of molecular sciences · 2024Article
- Exploring the Therapeutic Potential ofMolecules (Basel, Switzerland) · 2024Article
- Article
- Predictive identification and design of potent inhibitors targeting resistance-inducing candidate genes fromFrontiers in bioinformatics · 2024Article
- In Silico Identification of a Potential TNF-Alpha Binder Using a Structural Similarity: A Potential Drug Repurposing Approach to the Management of Alzheimer's Disease.BioMed research international · 2024Article
- Article
- Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation.Molecular diversity · 2023Article
- Virtual screening for potential discoidin domain receptor 1 (DDR1) inhibitors based on structural assessment.Molecular diversity · 2023Article
- Phytochemical Screening of Ultrasonic Extracts ofInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin 6 (IL-6) is a cytokine with various biological functions in immune regulation, hematopoiesis, and inflammation. Elevated IL-6 levels have been identified in several severe disorders such as sepsis, acute respiratory distress syndrome (ARDS), and most recently, COVID-19. The biological activity of IL-6 relies on interactions with its specific receptor, IL-6Rα, including the membrane-bound IL-6 receptor (mIL-6R) and the soluble IL-6 receptor (sIL-6R). Thus, inhibition of the interaction between these two proteins would be a potential treatment for IL-6 related diseases. To date, no orally available small-molecule drug has been approved. This study focuses on finding potential small molecules that can inhibit protein-protein interactions between IL-6 and its receptor IL-6Rα using its crystal structure (PDB ID: 5FUC). First, two pharmacophore models were constructed based on the interactions between key residues of IL-6 (Phe74, Phe78, Leu178, Arg179, Arg182) and IL-6Rα (Phe229, Tyr230, Glu277, Glu278, Phe279). A database of approximately 22 million compounds was screened using 3D-pharmacophore models, molecular docking models, and ADMET properties. By analyzing the interactive capability of successfully docked compounds with important amino acids, 12 potential ligands were selected for further analysis via molecular dynamics simulations. Based on the stability of the complexes, the high interactions rate of each ligand with the key residues of IL-6/IL-6Rα, and the low binding free energy calculation, two compounds ZINC83804241 and ZINC02997430, were identified as the most potential IL-6 inhibitor candidates. These results will pave the way for the design and optimization of more specific compounds to combat cytokine storm in severe coronavirus patients.
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