{"doi":"10.1101/2021.08.06.455424","title":"Small-molecule ligands can inhibit −1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses","abstract":"Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases since 2000 have high-lighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates −1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored a group of 6 small-molecule ligands, evaluating their activity against the frameshift signals from a panel of representative bat CoVs—the most likely source of future zoonoses—as well as SARS-CoV-2 and MERS-CoV. We found that whereas some ligands had notable activity against only a few of the frameshift signals, the serine protease inhibitor nafamostat suppressed −1 PRF significantly in several of them, while having limited to no effect on −1 PRF caused by frameshift signals from other viruses used as negative controls. These results suggest it is possible to find small-molecule ligands that inhibit −1 PRF specifically in a broad spectrum of CoVs, establishing the frameshift signal as a viable target for developing pan-coronaviral therapeutics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221386,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240541,"name":"Krishna Neupane","orcid":"0000-0003-1125-1924","position":1,"is_corresponding":false},{"id":821968,"name":"Sandaru M. Ileperuma","orcid":null,"position":2,"is_corresponding":false},{"id":821409,"name":"Matthew Halma","orcid":"0000-0003-2487-0636","position":3,"is_corresponding":false},{"id":240539,"name":"Jamie A. Kelly","orcid":"0000-0003-2416-2496","position":4,"is_corresponding":false},{"id":821410,"name":"Clarissa Halpern","orcid":"0000-0003-4230-1170","position":5,"is_corresponding":false},{"id":17814,"name":"Jonathan D. Dinman","orcid":"0000-0002-2402-9698","position":6,"is_corresponding":false},{"id":560521,"name":"Sarah Loerch","orcid":"0000-0002-1731-516X","position":7,"is_corresponding":false},{"id":240543,"name":"Michael T. Woodside","orcid":"0000-0003-4695-0397","position":8,"is_corresponding":false},{"id":243626,"name":"Sneha Munshi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:53:55.215284Z","pmid":null,"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":[]}