Related Experiment Video
Updated: Aug 23, 2025
An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions
Published on: March 14, 2016
LY3041658/ interleukin-8 complex structure as targets for IL-8 small molecule inhibitors discovery using a
T T N Tran1,2, Q H Tran1,2, Q T Nguyen1
1Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh, Vietnam.
Abstract:
Since interleukin-8 (IL-8/CXCL8) and its receptor, CXCR1 and CXCR2, were known in the early 1990s, biological pathways related to these proteins were proven to have high clinical value in cancer and inflammatory/autoimmune conditions treatment. Recently, IL-8 has been identified as biomarker for severe COVID-19 patients and COVID-19 prognosis. Boyles et al. (mAbs 12 (2020), pp. 1831880) have published a high-resolution X-ray crystal structure of the LY3041658 Fab in a complex human CXCL8. They described the ability to bind to IL-8 and the blocking of IL-8/its receptors interaction by the LY3041658 monoclonal antibody. Therefore, the study has been designed to identify potential small molecules inhibiting interleukin-8 by targeting LY3041658/IL-8 complex structure using an in silico approach. A structure‑based pharmacophore and molecular docking models of the protein active site cavity were generated to identify possible candidates, followed by virtual screening with the ZINC database. ADME analysis of hit compounds was also conducted. Molecular dynamics simulations were then performed to survey the behaviour and stability of the ligand-protein complexes. Furthermore, the MM/PBSA technique has been utilized to evaluate the free binding energy. The final data confirmed that one newly obtained compound, ZINC21882765, may serve as the best potential inhibitor for IL-8.
Insights
Researchers identified ZINC21882765 as a potential small molecule inhibitor for interleukin-8 (IL-8). This compound targets the LY3041658/IL-8 complex, offering a novel therapeutic strategy for IL-8-related conditions.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Chemistry
Background:
- Interleukin-8 (IL-8/CXCL8) and its receptors (CXCR1/CXCR2) are crucial in inflammatory and autoimmune diseases, cancer, and COVID-19 prognosis.
- A previously determined X-ray crystal structure of LY3041658 Fab complexed with human CXCL8 revealed its potential for blocking IL-8 interactions.
Purpose of the Study:
- To identify potential small molecules that inhibit interleukin-8 (IL-8) by targeting the LY3041658/IL-8 complex structure.
- To utilize an in silico approach for discovering novel IL-8 inhibitors.
Main Methods:
- Generated structure-based pharmacophore and molecular docking models of the IL-8 active site.
- Performed virtual screening using the ZINC database, followed by ADME analysis.
- Conducted molecular dynamics simulations and MM/PBSA calculations to assess binding energy and complex stability.
Main Results:
- Identified ZINC21882765 as a promising candidate inhibitor through in silico screening and analysis.
- Validated the binding affinity and stability of the ZINC21882765 compound with the IL-8 target.
Conclusions:
- ZINC21882765 demonstrates significant potential as a small molecule inhibitor for interleukin-8 (IL-8).
- This study provides a computational foundation for developing novel therapeutics targeting IL-8 pathways.
