{"doi":"10.3390/v14020177","title":"Identifying Inhibitors of −1 Programmed Ribosomal Frameshifting in a Broad Spectrum of Coronaviruses","abstract":"Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases in recent years have highlighted 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 whether small-molecule inhibitors of -1 PRF in SARS-CoV-2 also inhibited -1 PRF in a range of bat CoVs-the most likely source of future zoonoses. Six inhibitors identified in new and previous screens against SARS-CoV-2 were evaluated against the frameshift signals from a panel of representative bat CoVs as well as MERS-CoV. Some drugs had strong activity against subsets of these CoV-derived frameshift signals, while having limited to no effect on -1 PRF caused by frameshift signals from other viruses used as negative controls. Notably, the serine protease inhibitor nafamostat suppressed -1 PRF significantly for multiple CoV-derived frameshift signals. These results suggest it is possible to find small-molecule ligands that inhibit -1 PRF specifically in a broad spectrum of CoVs, establishing frameshift signals as a viable target for developing pan-coronaviral therapeutics.","journal":"Viruses","year":2022,"id":247124,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","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":70,"raw_metadata":null,"created_at":"2026-07-19T00:23:53.369530Z","pmid":"35215770","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":[]}