Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements.
Nucleic Acids Res
; 48(22): 12436-12452, 2020 12 16.
Article
in English
| MEDLINE | ID: covidwho-917707
ABSTRACT
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, â¼10.2% 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA, Viral
/
Genome, Viral
/
SARS-CoV-2
/
COVID-19
/
Nucleic Acid Conformation
Type of study:
Observational study
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Nucleic Acids Res
Year:
2020
Document Type:
Article
Affiliation country:
Nar
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