{"doi":"10.1101/2020.03.13.991083","title":"Structural and functional conservation of the programmed −1 ribosomal frameshift signal of SARS-CoV-2","abstract":"17 years after the SARS-CoV epidemic, the world is facing the COVID-19 pandemic. COVID-19 is caused by a coronavirus named SARS-CoV-2. Given the most optimistic projections estimating that it will take over a year to develop a vaccine, the best short-term strategy may lie in identifying virus-specific targets for small molecule interventions. All coronaviruses utilize a molecular mechanism called -1 PRF to control the relative expression of their proteins. Prior analyses of SARS-CoV revealed that it employs a structurally unique three-stemmed mRNA pseudoknot to stimulate high rates of -1 PRF, and that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity negatively impacts virus replication, suggesting that this molecular mechanism may be therapeutically targeted. Here we present a comparative analysis of the original SARS-CoV and SARS-CoV-2 frameshift signals. Structural and functional analyses revealed that both elements promote similar rates of -1 PRF and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablated -1 PRF activity. The upstream attenuator hairpin activity has also been functionally retained. Small-angle x-ray scattering indicated that the pseudoknots in SARS-CoV and SARS-CoV-2 had the same conformation. Finally, a small molecule previously shown to bind the SARS-CoV pseudoknot and inhibit -1 PRF was similarly effective against -1 PRF in SARS-CoV-2, suggesting that such frameshift inhibitors may provide promising lead compounds to counter the current pandemic.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119084,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240540,"name":"Alexandra N. Olson","orcid":"0000-0002-8533-1946","position":1,"is_corresponding":false},{"id":240541,"name":"Krishna Neupane","orcid":"0000-0003-1125-1924","position":2,"is_corresponding":false},{"id":243626,"name":"Sneha Munshi","orcid":null,"position":3,"is_corresponding":false},{"id":243627,"name":"Josue San Emeterio","orcid":null,"position":4,"is_corresponding":false},{"id":240542,"name":"Lois Pollack","orcid":"0000-0002-9366-4396","position":5,"is_corresponding":false},{"id":240543,"name":"Michael T. Woodside","orcid":"0000-0003-4695-0397","position":6,"is_corresponding":false},{"id":17814,"name":"Jonathan D. Dinman","orcid":"0000-0002-2402-9698","position":7,"is_corresponding":false},{"id":240539,"name":"Jamie A. Kelly","orcid":"0000-0003-2416-2496","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T23:14:08.313144Z","pmid":"32587971","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}