{"doi":"10.1128/jvi.00128-22","title":"Distinctive Roles of Furin and TMPRSS2 in SARS-CoV-2 Infectivity","abstract":"SARS-CoV-2, the etiological agent of COVID-19, has so far resulted in >6.1 million deaths worldwide. The spike protein (S) of the virus directs infection of the lungs and other tissues by binding the angiotensin-converting enzyme 2 (ACE2) receptor. For effective infection, the S protein is cleaved at two sites: S1/S2 and S2'. Cleavage at S1/S2 induces a conformational change favoring the S protein recognition by ACE2. The S2' cleavage is critical for triggering membrane fusion and virus entry into host cells. Our study highlights the complex dynamics of interaction between the S protein, ACE2, and the host proteases furin and TMPRSS2 during SARS-CoV-2 entry and suggests that the combination of a nontoxic furin inhibitor with a TMPRSS2 inhibitor significantly reduces viral entry in lung cells, as evidenced by an average synergistic ∼95% reduction of viral infection. This represents a powerful novel antiviral approach to reduce viral spread in individuals infected by SARS-CoV-2 or future related coronaviruses.","journal":"Journal of Virology","year":2022,"id":232496,"datarank":0.7917171988845778,"base_score":5.278114659230518,"endowment":5.278114659230518,"self_citation_contribution":0.7917171988845778,"citation_network_contribution":0.0,"self_endowment_contribution":0.7917171988845778,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":195,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"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":505721,"name":"Jaspreet Jain","orcid":null,"position":1,"is_corresponding":false},{"id":842702,"name":"Delia Susan‐Resiga","orcid":"0000-0002-4856-090X","position":2,"is_corresponding":false},{"id":281260,"name":"Ursula Andréo","orcid":"0000-0003-0438-0162","position":3,"is_corresponding":false},{"id":842703,"name":"Alexandra Evagelidis","orcid":"0009-0007-2331-591X","position":4,"is_corresponding":false},{"id":843370,"name":"Rabeb Mouna Derbali","orcid":null,"position":5,"is_corresponding":false},{"id":842704,"name":"David Huynh","orcid":"0009-0000-7750-6032","position":6,"is_corresponding":false},{"id":842705,"name":"Frédéric Dallaire","orcid":"0000-0002-0489-2523","position":7,"is_corresponding":false},{"id":843371,"name":"Mélanie Laporte","orcid":null,"position":8,"is_corresponding":false},{"id":842706,"name":"Adrien Delpal","orcid":"0000-0003-0598-7679","position":9,"is_corresponding":false},{"id":842707,"name":"Priscila Sutto‐Ortiz","orcid":"0000-0001-8672-690X","position":10,"is_corresponding":false},{"id":235143,"name":"Bruno Coutard","orcid":"0000-0002-2859-7123","position":11,"is_corresponding":false},{"id":842708,"name":"Claudine Mapa","orcid":"0000-0002-7928-8953","position":12,"is_corresponding":false},{"id":843372,"name":"Keith Wilcoxen","orcid":null,"position":13,"is_corresponding":false},{"id":235141,"name":"Étienne Decroly","orcid":"0000-0002-6046-024X","position":14,"is_corresponding":false},{"id":842709,"name":"Tram N. Q. Pham","orcid":"0000-0001-8238-9061","position":15,"is_corresponding":false},{"id":689257,"name":"Eric A. Cohen","orcid":"0000-0003-1269-3791","position":16,"is_corresponding":false},{"id":592307,"name":"Nabil G. Seidah","orcid":"0000-0001-6503-9342","position":17,"is_corresponding":false},{"id":843369,"name":"Rachid Essalmani","orcid":null,"position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:21:12.348693Z","pmid":"35343766","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":[]}