Are the integrin binding motifs within SARS CoV-2 spike protein and MHC class II alleles playing the key role in COVID-19?
COVID-19
MultiFOLD model
SARS CoV-2 spike protein
autoimmunity
deregulated coagulation
immune evasion
integrin binding motifs
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
01
03
2023
accepted:
22
05
2023
medline:
27
7
2023
pubmed:
26
7
2023
entrez:
26
7
2023
Statut:
epublish
Résumé
The previous studies on the RGD motif (aa403-405) within the SARS CoV-2 spike (S) protein receptor binding domain (RBD) suggest that the RGD motif binding integrin(s) may play an important role in infection of the host cells. We also discussed the possible role of two other integrin binding motifs that are present in S protein: LDI (aa585-587) and ECD (661-663), the motifs used by some other viruses in the course of infection. The MultiFOLD models for protein structure analysis have shown that the ECD motif is clearly accessible in the S protein, whereas the RGD and LDI motifs are partially accessible. Furthermore, the amino acids that are present in Epstein-Barr virus protein (EBV) gp42 playing very important role in binding to the HLA-DRB1 molecule and in the subsequent immune response evasion, are also present in the S protein heptad repeat-2. Our MultiFOLD model analyses have shown that these amino acids are clearly accessible on the surface in each S protein chain as monomers and in the homotrimer complex and bind to HLA-DRB1 β chain. Therefore, they may have the identical role in SARS CoV-2 immune evasion as in EBV infection. The prediction analyses of the MHC class II binding peptides within the S protein have shown that the RGD motif is present in the core 9-mer peptide IRGDEVRQI within the two HLA-DRB1*03:01 and HLA-DRB3*01.01 strong binding 15-mer peptides suggesting that RGD motif may be the potential immune epitope. Accordingly, infected HLA-DRB1*03:01 or HLA-DRB3*01.01 positive individuals may develop high affinity anti-RGD motif antibodies that react with the RGD motif in the host proteins, like fibrinogen, thrombin or von Willebrand factor, affecting haemostasis or participating in autoimmune disorders.
Identifiants
pubmed: 37492575
doi: 10.3389/fimmu.2023.1177691
pmc: PMC10364474
doi:
Substances chimiques
HLA-DRB1 Chains
0
spike protein, SARS-CoV-2
0
Spike Glycoprotein, Coronavirus
0
HLA-DRB3 Chains
0
Peptides
0
Amino Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1177691Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T018496/1
Pays : United Kingdom
Informations de copyright
Copyright © 2023 Gerencer and McGuffin.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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