{"doi":"10.1101/2020.06.22.165803","title":"CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2","abstract":"Abstract As the COVID-19 pandemic continues to spread, investigating the processes underlying the interactions between SARS-CoV-2 and its hosts is of high importance. Here, we report the identification of CD209L/L-SIGN and the related protein CD209/DC-SIGN as receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed prominent expression of CD209L in the lung and kidney epithelium and endothelium. Multiple biochemical assays using a purified recombinant SARS-CoV-2 spike receptor binding domain (S-RBD) or S1 encompassing both NTB and RBD and ectopically expressed CD209L and CD209 revealed that CD209L and CD209 interact with S-RBD. CD209L contains two N- glycosylation sequons, at sites N92 and N361, but we determined that only site N92 is occupied. Removal of the N -glycosylation at this site enhances the binding of S-RBD with CD209L. CD209L also interacts with ACE2, suggesting a role for heterodimerization of CD209L and ACE2 in SARS-CoV-2 entry and infection in cell types where both are present. Furthermore, we demonstrate that human endothelial cells are permissive to SARS-CoV-2 infection and interference with CD209L activity by knockdown strategy or with soluble CD209L inhibits virus entry. Our observations demonstrate that CD209L and CD209 serve as alternative receptors for SARS-CoV-2 in disease-relevant cell types, including the vascular system. This property is particularly important in tissues where ACE2 has low expression or is absent, and may have implications for antiviral drug development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118305,"datarank":0.7242470605953454,"base_score":4.8283137373023015,"endowment":4.8283137373023015,"self_citation_contribution":0.7242470605953454,"citation_network_contribution":0.0,"self_endowment_contribution":0.7242470605953454,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":124,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":364811,"name":"Wenqing Yin","orcid":"0000-0001-8123-4228","position":1,"is_corresponding":false},{"id":551220,"name":"Marc A. Napoleon","orcid":null,"position":2,"is_corresponding":false},{"id":232294,"name":"Ellen L. Suder","orcid":"0000-0001-9466-9204","position":3,"is_corresponding":false},{"id":551221,"name":"Jacob Berrigan","orcid":null,"position":4,"is_corresponding":false},{"id":495422,"name":"Qing Zhao","orcid":"0000-0003-2716-8383","position":5,"is_corresponding":false},{"id":232293,"name":"Judith Olejnik","orcid":"0000-0002-1748-7981","position":6,"is_corresponding":false},{"id":391250,"name":"Kevin Brown Chandler","orcid":"0000-0001-5514-9652","position":7,"is_corresponding":false},{"id":551222,"name":"Chaoshuang Xia","orcid":null,"position":8,"is_corresponding":false},{"id":104325,"name":"Jared Feldman","orcid":"0000-0002-4387-9954","position":9,"is_corresponding":false},{"id":104324,"name":"Blake M. Hauser","orcid":"0000-0002-0100-1684","position":10,"is_corresponding":false},{"id":106553,"name":"Timothy M. Caradonna","orcid":"0000-0001-7138-4441","position":11,"is_corresponding":false},{"id":104357,"name":"Aaron G. Schmidt","orcid":"0000-0003-3627-2553","position":12,"is_corresponding":false},{"id":69465,"name":"Suryaram Gummuluru","orcid":"0000-0002-8606-8481","position":13,"is_corresponding":false},{"id":551223,"name":"Elke Muhlberger","orcid":null,"position":14,"is_corresponding":false},{"id":551224,"name":"Vipul Chitalia","orcid":null,"position":15,"is_corresponding":false},{"id":391253,"name":"Catherine E. Costello","orcid":"0000-0003-1594-5122","position":16,"is_corresponding":false},{"id":495424,"name":"Nader Rahimi","orcid":"0000-0002-6745-1725","position":17,"is_corresponding":false},{"id":495421,"name":"Razie Amraei","orcid":"0000-0003-1969-6768","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:58.531532Z","pmid":"32607506","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":[]}