{"doi":"10.1016/j.celrep.2022.110829","title":"Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant","abstract":"We report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement during the coronavirus disease 2019 (COVID-19) pandemic. Delta SARS-CoV-2 efficiently outcompetes the Alpha variant in human lung epithelial cells and primary human airway tissues. The Delta spike mutation P681R is located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduces the replication of the Delta variant to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhances the cleavage of the full-length spike to S1 and S2, which could improve cell-surface-mediated virus entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the cleavage of the Alpha spike is reduced compared with the Delta spike. Our results suggest P681R as a key mutation in enhancing Delta-variant replication via increased S1/S2 cleavage.","journal":"Cell Reports","year":2022,"id":231833,"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":393,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":240711,"name":"Jianying Liu","orcid":"0009-0006-2040-1188","position":1,"is_corresponding":false},{"id":105304,"name":"Bryan A. Johnson","orcid":"0000-0002-8999-1255","position":2,"is_corresponding":false},{"id":105303,"name":"Hongjie Xia","orcid":"0000-0002-2520-7038","position":3,"is_corresponding":false},{"id":105312,"name":"Zhiqiang Ku","orcid":"0000-0001-8347-0013","position":4,"is_corresponding":false},{"id":108475,"name":"Craig Schindewolf","orcid":"0000-0002-9804-2246","position":5,"is_corresponding":false},{"id":225076,"name":"Steven G. Widen","orcid":"0000-0002-6512-363X","position":6,"is_corresponding":false},{"id":105313,"name":"Zhiqiang An","orcid":"0000-0001-9309-2335","position":7,"is_corresponding":false},{"id":105319,"name":"Scott C. Weaver","orcid":"0000-0001-8016-8556","position":8,"is_corresponding":false},{"id":105316,"name":"Vineet D. Menachery","orcid":"0000-0001-8803-7606","position":9,"is_corresponding":false},{"id":105317,"name":"Xuping Xie","orcid":"0000-0003-0918-016X","position":10,"is_corresponding":false},{"id":38215,"name":"Pei‐Yong Shi","orcid":"0000-0001-5553-1616","position":11,"is_corresponding":false},{"id":839711,"name":"Yang Liu","orcid":"0000-0002-1312-6281","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:20:51.245255Z","pmid":"35550680","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":[]}