In-silico and in-vitro studies revealed alpha-amyrin as a potent pnhibitor of TLR2 for the therapeutics of bacterial infection and sepsis

Alpha-amyrin as an effective inhibitor of TLR2

Authors

  • Thoraya A-Elgader Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Mohamed Abd Ellatif 1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia. 2Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
  • Basiouny El-Gamal Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Khalid Ali Nasif 1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia. 3Department of Medical Biochemistry, Faculty of Medicine, Minia University, Minia, Egypt
  • Safaa Omer 1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Muniera Mohieldeen 1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Ayyub A. Patel Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Mohammed Amanullah 1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Arshi Malik CQRL BITS LLP, Chennai, India.
  • Ahmed A. Mahfouz 5Department of Family and Community Medicine, King Khalid University, Abha, Saudi Arabia 6Department of Epidemology, High Institute of Public Health, Alexandria University, Egypt
  • Ayman H. Shaamash Department of Obstetrics and Gynecology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
  • Awad S. Alsamghan Department of Family and Community Medicine, King Khalid University, Abha, Saudi Arabia

Keywords:

Alpha-amyrin, bacterial infection, HEK-293, HUVECs, sepsis, toll like receptor 2 (TLR2)

Abstract

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

Published

2024-09-04

Issue

Vol. 70 No. 6 (2024)

Section

Original Research Articles

License

Copyright (c) 2024 Thoraya A-Elgader, Mohamed Abd Ellatif, Basiouny El-Gamal Basiouny El-Gamal, Khalid Ali Nasif, Safaa Omer, Muniera Mohieldeen, Ayyub A. Patel, Mohammed Amanullah, Arshi Malik, Ahmed A. Mahfouz, Ayman H. Shaamash, Awad S. Alsamghan

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.