{"doi":"10.1101/2020.08.13.243303","title":"Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor Ace2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors will not prevent viral spread.</jats:p>","journal":null,"year":null,"id":620726,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":838861,"name":"Donna L. Mallery","orcid":"0000-0003-2713-5215","position":1,"is_corresponding":false},{"id":1026925,"name":"Anna Albecka","orcid":"0000-0002-3672-5498","position":2,"is_corresponding":false},{"id":1602502,"name":"Lawrence Welch","orcid":null,"position":3,"is_corresponding":false},{"id":1602503,"name":"Jérôme Cattin-Ortolá","orcid":null,"position":4,"is_corresponding":false},{"id":1602504,"name":"Jakub Luptak","orcid":null,"position":5,"is_corresponding":false},{"id":1602506,"name":"David Paul","orcid":null,"position":6,"is_corresponding":false},{"id":1507067,"name":"Harvey T. McMahon","orcid":null,"position":7,"is_corresponding":false},{"id":1482,"name":"Ian G. Goodfellow","orcid":"0000-0002-9483-510X","position":8,"is_corresponding":false},{"id":1080084,"name":"Andrew Carter","orcid":"0009-0006-7953-8998","position":9,"is_corresponding":false},{"id":1602510,"name":"Sean Munro","orcid":null,"position":10,"is_corresponding":false},{"id":859451,"name":"Leo C. James","orcid":"0000-0003-2131-0334","position":11,"is_corresponding":false},{"id":838859,"name":"Guido Papa","orcid":"0000-0002-5215-0014","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor Ace2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors will not prevent viral spread.</jats:p>","is_dataset_classified":null,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W3048584557","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2020,"count":8},{"year":2021,"count":18},{"year":2022,"count":7},{"year":2023,"count":6},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/08/19/2020.08.13.243303.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/08/19/2020.08.13.243303.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2020.08.13.243303","host_type":"publisher"},{"url":"https://doi.org/10.1101/2020.08.13.243303","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/handle/1810/317198","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/handle/1810/318458","host_type":"repository"},{"url":"https://doi.org/10.17863/cam.64311","host_type":"repository"},{"url":"https://doi.org/10.17863/cam.65572","host_type":"repository"},{"url":"https://europepmc.org/article/PPR/PPR200842","host_type":"Europe_PMC"},{"url":"https://europepmc.org/api/fulltextRepo?pprId=PPR200842&type=FILE&fileName=EMS92882-pdf.pdf&mimeType=application/pdf","host_type":"Europe_PMC"}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","CRISPR and Genetic Engineering","Animal Virus Infections Studies"],"mesh_terms":[],"keywords":["Furin","Cell fusion","Syncytium","Virology","Virus","Lipid bilayer fusion","Infectivity","Coronavirus","Biology","Cleavage (geology)","Cell","HEK 293 cells","Cell biology","Mutant","Cell culture","Gene","Coronavirus disease 2019 (COVID-19)","Biochemistry","Genetics","Enzyme"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T11:57:42.943873Z","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":[]}