{"doi":"10.1371/journal.pbio.3001805","title":"LRRC15 inhibits SARS-CoV-2 cellular entry in trans","abstract":"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory attachment factor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single-cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not coexpressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory attachment factor for SARS-CoV-2 that regulates viral entry in trans.","journal":"PLoS Biology","year":2022,"id":252938,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"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":254235,"name":"Ryan D. Chow","orcid":"0000-0002-1872-6307","position":1,"is_corresponding":false},{"id":808383,"name":"Mario A. Peña-Hernández","orcid":null,"position":2,"is_corresponding":false},{"id":313787,"name":"Li Zhang","orcid":"0000-0003-4803-3891","position":3,"is_corresponding":false},{"id":190932,"name":"Skylar A. Loeb","orcid":"0000-0003-0213-5163","position":4,"is_corresponding":false},{"id":556750,"name":"Eui‐Young So","orcid":null,"position":5,"is_corresponding":false},{"id":556107,"name":"Olin D. Liang","orcid":"0000-0002-2266-6722","position":6,"is_corresponding":false},{"id":861705,"name":"Ping Ren","orcid":"0000-0002-6507-5180","position":7,"is_corresponding":false},{"id":60778,"name":"Sidi Chen","orcid":"0000-0002-3819-5005","position":8,"is_corresponding":false},{"id":107022,"name":"Craig B. Wilen","orcid":"0000-0003-2495-9403","position":9,"is_corresponding":false},{"id":680249,"name":"Sanghyun Lee","orcid":"0000-0002-0736-1648","position":10,"is_corresponding":false},{"id":807707,"name":"Jaewon Song","orcid":"0000-0002-9387-1942","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:24:50.819822Z","pmid":"36228039","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":[]}