Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication?
Non-B nucleic acids structures have arisen as key contributors to genetic variation in SARS-CoV-2. Herein, we investigated the presence of defining spike protein mutations falling within inverted repeats (IRs) for 18 SARS-CoV-2 variants, discussed the potential roles of G-quadruplexes (G4s) in SARS-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/1/157 |
| _version_ | 1797442048029097984 |
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| author | Stefan Bidula Václav Brázda |
| author_facet | Stefan Bidula Václav Brázda |
| author_sort | Stefan Bidula |
| collection | DOAJ |
| description | Non-B nucleic acids structures have arisen as key contributors to genetic variation in SARS-CoV-2. Herein, we investigated the presence of defining spike protein mutations falling within inverted repeats (IRs) for 18 SARS-CoV-2 variants, discussed the potential roles of G-quadruplexes (G4s) in SARS-CoV-2 biology, and identified potential pseudoknots within the SARS-CoV-2 genome. Surprisingly, there was a large variation in the number of defining spike protein mutations arising within IRs between variants and these were more likely to occur in the stem region of the predicted hairpin stem-loop secondary structure. Notably, mutations implicated in ACE2 binding and propagation (e.g., ΔH69/V70, N501Y, and D614G) were likely to occur within IRs, whilst mutations involved in antibody neutralization and reduced vaccine efficacy (e.g., T19R, ΔE156, ΔF157, R158G, and G446S) were rarely found within IRs. We also predicted that RNA pseudoknots could predominantly be found within, or next to, 29 mutations found in the SARS-CoV-2 spike protein. Finally, the Omicron variants BA.2, BA.4, BA.5, BA.2.12.1, and BA.2.75 appear to have lost two of the predicted G4-forming sequences found in other variants. These were found in <i>nsp2</i> and the sequence complementary to the conserved stem-loop II-like motif (S2M) in the 3′ untranslated region (UTR). Taken together, non-B nucleic acids structures likely play an integral role in SARS-CoV-2 evolution and genetic diversity. |
| first_indexed | 2024-03-09T12:35:59Z |
| format | Article |
| id | doaj.art-6f3edca026a749bd9aed1db9236baeda |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T12:35:59Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-6f3edca026a749bd9aed1db9236baeda2023-11-30T22:24:26ZengMDPI AGGenes2073-44252023-01-0114115710.3390/genes14010157Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication?Stefan Bidula0Václav Brázda1School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UKInstitute of Biophysics of the Czech Academy of Sciences, 61265 Brno, Czech RepublicNon-B nucleic acids structures have arisen as key contributors to genetic variation in SARS-CoV-2. Herein, we investigated the presence of defining spike protein mutations falling within inverted repeats (IRs) for 18 SARS-CoV-2 variants, discussed the potential roles of G-quadruplexes (G4s) in SARS-CoV-2 biology, and identified potential pseudoknots within the SARS-CoV-2 genome. Surprisingly, there was a large variation in the number of defining spike protein mutations arising within IRs between variants and these were more likely to occur in the stem region of the predicted hairpin stem-loop secondary structure. Notably, mutations implicated in ACE2 binding and propagation (e.g., ΔH69/V70, N501Y, and D614G) were likely to occur within IRs, whilst mutations involved in antibody neutralization and reduced vaccine efficacy (e.g., T19R, ΔE156, ΔF157, R158G, and G446S) were rarely found within IRs. We also predicted that RNA pseudoknots could predominantly be found within, or next to, 29 mutations found in the SARS-CoV-2 spike protein. Finally, the Omicron variants BA.2, BA.4, BA.5, BA.2.12.1, and BA.2.75 appear to have lost two of the predicted G4-forming sequences found in other variants. These were found in <i>nsp2</i> and the sequence complementary to the conserved stem-loop II-like motif (S2M) in the 3′ untranslated region (UTR). Taken together, non-B nucleic acids structures likely play an integral role in SARS-CoV-2 evolution and genetic diversity.https://www.mdpi.com/2073-4425/14/1/157SARS-CoV-2inverted repeatsG-quadruplexpseudoknotspike proteinmutation |
| spellingShingle | Stefan Bidula Václav Brázda Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication? Genes SARS-CoV-2 inverted repeats G-quadruplex pseudoknot spike protein mutation |
| title | Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication? |
| title_full | Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication? |
| title_fullStr | Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication? |
| title_full_unstemmed | Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication? |
| title_short | Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication? |
| title_sort | genomic analysis of non b nucleic acids structures in sars cov 2 potential key roles for these structures in mutability translation and replication |
| topic | SARS-CoV-2 inverted repeats G-quadruplex pseudoknot spike protein mutation |
| url | https://www.mdpi.com/2073-4425/14/1/157 |
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