Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysis
Introduction: Computational studies were performed to investigate the unknown status of endosomal and cell surface receptors in SARS-CoV-2 infection. The interactions between Toll-like receptors (TLRs)- 4/7/8/9 or ACE2 receptor and different SARS-CoV-2 variants were investigated. Methods: The RNA m...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tabriz University of Medical Sciences
2024-07-01
|
| Series: | BioImpacts |
| Subjects: | |
| Online Access: | https://bi.tbzmed.ac.ir/PDF/bi-14-30150.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832595635701809152 |
|---|---|
| author | Azadeh Zahmatkesh Elham Salmasi Reza Gholizadeh |
| author_facet | Azadeh Zahmatkesh Elham Salmasi Reza Gholizadeh |
| author_sort | Azadeh Zahmatkesh |
| collection | DOAJ |
| description | Introduction: Computational studies were performed to investigate the unknown status of endosomal and cell surface receptors in SARS-CoV-2 infection. The interactions between Toll-like receptors (TLRs)- 4/7/8/9 or ACE2 receptor and different SARS-CoV-2 variants were investigated. Methods: The RNA motifs for TLR7, TLR8 and a CpG motif for TLR9 were analyzed in different variants. Molecular docking and molecular dynamics (MD) simulations were performed to investigate receptor-ligand interactions. Results: The number of motifs recognized by TLR7/8/9 in the Alpha, Delta and Iranian variants was lower than in the wild type (WT). Docking analysis revealed that the Alpha, Delta and some Iranian spike variants had a higher affinity for ACE2 and TLR4 than the WT, which may account for their higher transmission rate. The MD simulation also showed differences in stability and structure size between the variants and the WT, indicating potential variations in viral load. Conclusion: It appears that Alpha and some Iranian isolates are the variants of concern due to their higher transmissibility and rapid spread. The Delta mutant is also a variant of concern, not only because of its closer interaction with ACE2, but also with TLR4. Our results emphasize the importance of ACE2 and TLR4, rather than endosomal TLRs, in mediating the effects of different viral mutations and suggest their potential therapeutic applications. |
| format | Article |
| id | doaj-art-af34849b458043e58095814453dedd11 |
| institution | Kabale University |
| issn | 2228-5652 2228-5660 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | BioImpacts |
| spelling | doaj-art-af34849b458043e58095814453dedd112025-01-18T10:01:47ZengTabriz University of Medical SciencesBioImpacts2228-56522228-56602024-07-01144301503015010.34172/bi.2024.30150bi-30150Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysisAzadeh Zahmatkesh0Elham Salmasi1Reza Gholizadeh2Department of Anaerobic Bacterial Vaccines Research and Production, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, IranDepartment of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, PR ChinaDepartment of Catalysis and Chemical Reaction Engineering, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, SloveniaIntroduction: Computational studies were performed to investigate the unknown status of endosomal and cell surface receptors in SARS-CoV-2 infection. The interactions between Toll-like receptors (TLRs)- 4/7/8/9 or ACE2 receptor and different SARS-CoV-2 variants were investigated. Methods: The RNA motifs for TLR7, TLR8 and a CpG motif for TLR9 were analyzed in different variants. Molecular docking and molecular dynamics (MD) simulations were performed to investigate receptor-ligand interactions. Results: The number of motifs recognized by TLR7/8/9 in the Alpha, Delta and Iranian variants was lower than in the wild type (WT). Docking analysis revealed that the Alpha, Delta and some Iranian spike variants had a higher affinity for ACE2 and TLR4 than the WT, which may account for their higher transmission rate. The MD simulation also showed differences in stability and structure size between the variants and the WT, indicating potential variations in viral load. Conclusion: It appears that Alpha and some Iranian isolates are the variants of concern due to their higher transmissibility and rapid spread. The Delta mutant is also a variant of concern, not only because of its closer interaction with ACE2, but also with TLR4. Our results emphasize the importance of ACE2 and TLR4, rather than endosomal TLRs, in mediating the effects of different viral mutations and suggest their potential therapeutic applications.https://bi.tbzmed.ac.ir/PDF/bi-14-30150.pdftlr4tlr7/8/9motifalpha variantdelta varianttransmission |
| spellingShingle | Azadeh Zahmatkesh Elham Salmasi Reza Gholizadeh Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysis BioImpacts tlr4 tlr7/8/9 motif alpha variant delta variant transmission |
| title | Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysis |
| title_full | Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysis |
| title_fullStr | Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysis |
| title_full_unstemmed | Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysis |
| title_short | Interaction of toll-like receptors and ACE-2 with different variants of SARS-CoV-2: A computational analysis |
| title_sort | interaction of toll like receptors and ace 2 with different variants of sars cov 2 a computational analysis |
| topic | tlr4 tlr7/8/9 motif alpha variant delta variant transmission |
| url | https://bi.tbzmed.ac.ir/PDF/bi-14-30150.pdf |
| work_keys_str_mv | AT azadehzahmatkesh interactionoftolllikereceptorsandace2withdifferentvariantsofsarscov2acomputationalanalysis AT elhamsalmasi interactionoftolllikereceptorsandace2withdifferentvariantsofsarscov2acomputationalanalysis AT rezagholizadeh interactionoftolllikereceptorsandace2withdifferentvariantsofsarscov2acomputationalanalysis |