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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/8939| Genome-wide mapping of therapeutically-relevant SARS-CoV-2 RNA structures | |
| Ilaria Manfredonia NITHIN C Almudena Ponce-Salvatierra Pritha Ghosh Tomasz Wirecki Tycho Marinus Natacha Ogando Eric Snijder Martijn van Hemert Janusz Bujnicki Danny Incarnato | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2020.06.15.151647 | |
| https://www.biorxiv.org/content/10.1101/2020.06.15.151647v1 | |
| SARS-CoV-2 is a betacoronavirus with a linear single-stranded, positive-sense RNA genome of ∼30 kb, whose outbreak caused the still 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 structural elements within coronavirus RNA genomes have been identified to date. Here, we performed RNA structure probing by SHAPE-MaP to obtain a single-base resolution secondary structure map of the full SARS-CoV-2 coronavirus genome. The SHAPE-MaP probing data recapitulate the previously described coronavirus RNA elements (5′ UTR, ribosomal frameshifting element, and 3′ UTR), and reveal new structures. Secondary structure-restrained 3D modeling of highly-structured regions across the SARS-CoV-2 genome allowed for the identification of several putative druggable pockets. Furthermore, ∼8% of the identified structure elements show significant covariation among SARS-CoV-2 and other coronaviruses, hinting at their functionally-conserved role. In addition, we identify a set of persistently single-stranded regions having 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. | |
| bioRxiv | |
| 15-06-2020 | |
| Preimpreso | |
| Inglés | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Materiales de Consulta y Comunicados Técnicos |
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| Genome-wide mapping of therapeutically-relevant SARS-CoV-2 RNA structures.pdf | 24.81 MB | Adobe PDF | Visualizar/Abrir |