The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements
Open accessAbstract
SARS-CoV-2 is a betacoronavirus with a linear single-stranded, positive-sense RNA genome, whose outbreak caused the ongoing COVID-19 pandemic. The ability of coronaviruses to rapidly evolve, adapt, and cross species barriers makes the development of effective and durable therapeutic strategies a challenging and urgent need. As for other RNA viruses, genomic RNA structures are expected to play crucial roles in several steps of the coronavirus replication cycle. Despite this, only a handful of functionally-conserved coronavirus structural RNA elements have been identified to date. Here, we performed RNA structure probing to obtain single-base resolution secondary structure maps of the full SARS-CoV-2 coronavirus genome both in vitro and in living infected cells. Probing data recapitulate the previously described coronavirus RNA elements (5′ UTR and s2m), and reveal new structures. Of these, ∼10.2% show significant covariation among SARS-CoV-2 and other coronaviruses, hinting at their functionally-conserved role. Secondary structure-restrained 3D modeling of these segments further allowed for the identification of putative druggable pockets. In addition, we identify a set of single-stranded segments in vivo, showing high sequence conservation, suitable for the development of antisense oligonucleotide therapeutics. Collectively, our work lays the foundation for the development of innovative RNA-targeted therapeutic strategies to fight SARS-related infections.
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Cites
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Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Leppek, K., Byeon, G. W., Kladwang, W., Wayment-Steele, H. K., Kerr, C. H., Xu, A. F., Kim, D. S., Topkar, V. V., Choe, C., Rothschild, D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28776-w · Cited by 399
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
Leppek, K., Byeon, G. W., Kladwang, W., Wayment-Steele, H. K., Kerr, C. H., Xu, A. F., Kim, D. S., Topkar, V. V., Choe, C., Rothschild, D., et al. (2021) · doi:10.1101/2021.03.29.437587 · Cited by 399
Zhang, K., Zheludev, I. N., Hagey, R. J., Haslecker, R., Hou, Y. J., Kretsch, R., Pintilie, G. D., Rangan, R., Kladwang, W., Li, S., et al. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-021-00653-y · Cited by 189
Secondary structure of the SARS-CoV-2 5’-UTR
Miao, Z., Tidu, A., Eriani, G., & Martin, F. (2021) · RNA Biology · doi:10.1080/15476286.2020.1814556 · Cited by 156
Metadata
- Authors
- Manfredonia, I., Nithin, C., Ponce-Salvatierra, A., Ghosh, P., Wirecki, T. K., Marinus, T., Ogando, N. S., Snijder, E. J., van Hemert, M. J., Bujnicki, J. M., & Incarnato, D.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-11-10
- Volume
- 48
- Issue
- 22
- Pages
- 12436-12452
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W3098049011
- Cited by
- 282
- References
- 61
- FWCI
- 12.31
- Type
- journal article
- Language
- en
- Open access
- gold
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- Manfredonia, I., Nithin, C., Ponce-Salvatierra, A., Ghosh, P., Wirecki, T. K., Marinus, T., Ogando, N. S., Snijder, E. J., van Hemert, M. J., Bujnicki, J. M., & Incarnato, D. (2020). Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa1053
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