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.
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| http://dx.doi.org/10.34172/bi.2024.30150 | DOI Listing |
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