Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns
Since the onset of pandemic in 2019, SARS-CoV-2 has diverged into numerous variants driven by antigenic and infectivity-oriented selection. Some variants have accumulated fitness-enhancing mutations, evaded immunity and spread despite global vaccination campaigns. The spike (S) glycoprotein of SARS-...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | European Journal of Cell Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933522000784 |
| _version_ | 1811188618916528128 |
|---|---|
| author | Filips Peisahovics Mohammed A. Rohaim Muhammad Munir |
| author_facet | Filips Peisahovics Mohammed A. Rohaim Muhammad Munir |
| author_sort | Filips Peisahovics |
| collection | DOAJ |
| description | Since the onset of pandemic in 2019, SARS-CoV-2 has diverged into numerous variants driven by antigenic and infectivity-oriented selection. Some variants have accumulated fitness-enhancing mutations, evaded immunity and spread despite global vaccination campaigns. The spike (S) glycoprotein of SARS-CoV-2 demonstrated the greatest immunogenicity and amino acid substitution diversity owing to its importance in the interaction with human angiotensin receptor 2 (hACE2). The S protein consistently emerges as an amino acid substitution (AAS) hotspot in all six lineages, however, in Omicron this enrichment is significantly higher. This study attempts to design and validate a method of mapping S-protein substitution profile across variants to identify the conserved and AAS regions. A substitution matrix was created based on publicly available databases, and the substitution localization was illustrated on a cryo-electron microscopy generated S-protein model. Our analyses indicated that the diversity of N-terminal (NTD) and receptor-binding (RBD) domains exceeded that of any other regions but still contained extended low substitution density regions particularly considering significantly broader substitution profiles of Omicron BA.2 and BA.4/5. Finally, the substitution matrix was compared to a random sample alignment of variant sequences, revealing discrepancies. Therefore, it was suggested to improve matrix accuracy by processing a large number of S-protein sequences using an automated algorithm. Several critical immunogenic and receptor-interacting residues were identified in the conserved regions within NTD and RBD. In conclusion, the structural and topological analysis of S proteins of SARS-CoV-2 variants highlight distinctive amino acid substitution patterns which may be foundational in predicting future variants. |
| first_indexed | 2024-04-11T14:23:01Z |
| format | Article |
| id | doaj.art-2306c7ffd08e4264a2cd99c10fd61a12 |
| institution | Directory Open Access Journal |
| issn | 0171-9335 |
| language | English |
| last_indexed | 2024-04-11T14:23:01Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj.art-2306c7ffd08e4264a2cd99c10fd61a122022-12-22T04:19:00ZengElsevierEuropean Journal of Cell Biology0171-93352022-09-011014151275Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patternsFilips Peisahovics0Mohammed A. Rohaim1Muhammad Munir2Division of Biomedical and Life Sciences, Lancaster University, Lancaster, Lancashire LA1 4YG, United KingdomDivision of Biomedical and Life Sciences, Lancaster University, Lancaster, Lancashire LA1 4YG, United KingdomCorrespondence to: Lancaster University, Lancaster, United Kingdom.; Division of Biomedical and Life Sciences, Lancaster University, Lancaster, Lancashire LA1 4YG, United KingdomSince the onset of pandemic in 2019, SARS-CoV-2 has diverged into numerous variants driven by antigenic and infectivity-oriented selection. Some variants have accumulated fitness-enhancing mutations, evaded immunity and spread despite global vaccination campaigns. The spike (S) glycoprotein of SARS-CoV-2 demonstrated the greatest immunogenicity and amino acid substitution diversity owing to its importance in the interaction with human angiotensin receptor 2 (hACE2). The S protein consistently emerges as an amino acid substitution (AAS) hotspot in all six lineages, however, in Omicron this enrichment is significantly higher. This study attempts to design and validate a method of mapping S-protein substitution profile across variants to identify the conserved and AAS regions. A substitution matrix was created based on publicly available databases, and the substitution localization was illustrated on a cryo-electron microscopy generated S-protein model. Our analyses indicated that the diversity of N-terminal (NTD) and receptor-binding (RBD) domains exceeded that of any other regions but still contained extended low substitution density regions particularly considering significantly broader substitution profiles of Omicron BA.2 and BA.4/5. Finally, the substitution matrix was compared to a random sample alignment of variant sequences, revealing discrepancies. Therefore, it was suggested to improve matrix accuracy by processing a large number of S-protein sequences using an automated algorithm. Several critical immunogenic and receptor-interacting residues were identified in the conserved regions within NTD and RBD. In conclusion, the structural and topological analysis of S proteins of SARS-CoV-2 variants highlight distinctive amino acid substitution patterns which may be foundational in predicting future variants.http://www.sciencedirect.com/science/article/pii/S0171933522000784VirusesCell biologyVariantsStructural biologyEvolution |
| spellingShingle | Filips Peisahovics Mohammed A. Rohaim Muhammad Munir Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns European Journal of Cell Biology Viruses Cell biology Variants Structural biology Evolution |
| title | Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns |
| title_full | Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns |
| title_fullStr | Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns |
| title_full_unstemmed | Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns |
| title_short | Structural topological analysis of spike proteins of SARS-CoV-2 variants of concern highlight distinctive amino acid substitution patterns |
| title_sort | structural topological analysis of spike proteins of sars cov 2 variants of concern highlight distinctive amino acid substitution patterns |
| topic | Viruses Cell biology Variants Structural biology Evolution |
| url | http://www.sciencedirect.com/science/article/pii/S0171933522000784 |
| work_keys_str_mv | AT filipspeisahovics structuraltopologicalanalysisofspikeproteinsofsarscov2variantsofconcernhighlightdistinctiveaminoacidsubstitutionpatterns AT mohammedarohaim structuraltopologicalanalysisofspikeproteinsofsarscov2variantsofconcernhighlightdistinctiveaminoacidsubstitutionpatterns AT muhammadmunir structuraltopologicalanalysisofspikeproteinsofsarscov2variantsofconcernhighlightdistinctiveaminoacidsubstitutionpatterns |