PropertyValue
?: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.
?:creator
?:doi
  • 10.1371/journal.pcbi.1008603
?:doi
?:journal
  • PLoS_Comput_Biol
?:license
  • cc-by
?:pdf_json_files
  • document_parses/pdf_json/b08b0a5408971112444f4b44fdb373a07ebe3c93.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7845960.xml.json
?:pmcid
?:pmid
?:pmid
  • 33465066.0
?:publication_isRelatedTo_Disease
?:sha_id
?:source
  • Medline; PMC
?:title
  • Modeling the structure of the frameshift-stimulatory pseudoknot in SARS-CoV-2 reveals multiple possible conformers
?:type
?:year
  • 2021-01-19

Metadata

Anon_0  
expand all