Modeling the structure of the frameshift-stimulatory pseudoknot in SARS-CoV-2 reveals multiple possible conformers.
PLoS Comput Biol
; 17(1): e1008603, 2021 01.
Article
in English
| MEDLINE | ID: covidwho-1035017
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The coronavirus causing the COVID-19 pandemic, SARS-CoV-2, uses -1 programmed ribosomal frameshifting (-1 PRF) to control the relative expression of viral proteins. As modulating -1 PRF can inhibit viral replication, the RNA pseudoknot stimulating -1 PRF may be a fruitful target for therapeutics treating COVID-19. We modeled the unusual 3-stem structure of the stimulatory pseudoknot of SARS-CoV-2 computationally, using multiple blind structural prediction tools followed by µs-long molecular dynamics simulations. The results were compared for consistency with nuclease-protection assays and single-molecule force spectroscopy measurements of the SARS-CoV-1 pseudoknot, to determine the most likely conformations. We found several possible conformations for the SARS-CoV-2 pseudoknot, all having an extended stem 3 but with different packing of stems 1 and 2. Several conformations featured rarely-seen threading of a single strand through junctions formed between two helices. These structural models may help interpret future experiments and support efforts to discover ligands inhibiting -1 PRF in SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Frameshifting, Ribosomal
/
SARS-CoV-2
/
Nucleic Acid Conformation
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
PLoS Comput Biol
Journal subject:
Biology
/
Medical Informatics
Year:
2021
Document Type:
Article
Affiliation country:
Journal.pcbi.1008603
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