{"doi":"10.1101/2021.01.05.425478","title":"Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19","abstract":"COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP- inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214478,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":634680,"name":"Bing Ma","orcid":"0000-0002-5640-283X","position":1,"is_corresponding":false},{"id":634682,"name":"Chuan He","orcid":"0000-0002-6461-7515","position":2,"is_corresponding":false},{"id":634681,"name":"Bedia Akosman","orcid":"0000-0001-6571-546X","position":3,"is_corresponding":false},{"id":647544,"name":"Yang Zhou","orcid":"0000-0001-6867-6443","position":4,"is_corresponding":false},{"id":556104,"name":"Chang Min Lee","orcid":"0000-0003-2567-5533","position":5,"is_corresponding":false},{"id":94964,"name":"Wafik S. El‐Deiry","orcid":"0000-0002-9577-8266","position":6,"is_corresponding":false},{"id":556098,"name":"Kelsey E. Huntington","orcid":"0000-0002-5810-8220","position":7,"is_corresponding":false},{"id":556107,"name":"Olin D. Liang","orcid":"0000-0002-2266-6722","position":8,"is_corresponding":false},{"id":670684,"name":"Jason T. Machan","orcid":"0000-0003-2048-4914","position":9,"is_corresponding":false},{"id":397129,"name":"Min‐Jong Kang","orcid":"0000-0003-3245-144X","position":10,"is_corresponding":false},{"id":670685,"name":"Hyeon Jun Shin","orcid":"0000-0002-2150-5011","position":11,"is_corresponding":false},{"id":608819,"name":"Emiko Mizoguchi","orcid":"0000-0002-4019-0617","position":12,"is_corresponding":false},{"id":381134,"name":"Chun Geun Lee","orcid":"0000-0002-9514-3658","position":13,"is_corresponding":false},{"id":59657,"name":"Jack A. Elias","orcid":"0000-0002-3124-8557","position":14,"is_corresponding":false},{"id":556103,"name":"Suchitra Kamle","orcid":"0000-0001-9847-1211","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-18T23:52:46.604690Z","pmid":"33442679","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":[]}