{"doi":"10.1101/2022.09.09.507342","title":"Targeting intracellular Neu1 for Coronavirus Infection Treatment","abstract":"Summary There are no effective therapies for COVID-19 or antivirals against SARS-CoV-2. Furthermore, current vaccines appear less efficacious for new SARS-CoV-2 variants. Thus, there is an urgent need to better understand the virulence mechanisms of SARS-CoV-2 and the host response to develop therapeutic agents. Here, we show host Neu1 regulates coronavirus replication by controlling sialylation on coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins in COVID-19 patients and in coronavirus HCoV-OC43-infected cells were heavily sialylated; this sialylation controlled the RNA binding activity and replication of coronavirus. Neu1 overexpression increased HCoV-OC43 replication, whereas Neu1 knockdown reduced HCoV-OC43 replication. Moreover, a newly developed Neu1 inhibitor, Neu5Ac2en-OAcOMe, selectively targeted intracellular sialidase, which dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. Our findings suggest that Neu1 inhibitors could be used to limit SARS-CoV-2 replication in patients with COVID-19, making Neu1 a potential therapeutic target for COVID-19 and future coronavirus pandemics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304274,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"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":435459,"name":"Yin Wu","orcid":"0000-0001-7369-8612","position":1,"is_corresponding":false},{"id":861204,"name":"Isaac Turan","orcid":null,"position":2,"is_corresponding":false},{"id":861202,"name":"Joseph M. Keil","orcid":null,"position":3,"is_corresponding":false},{"id":308609,"name":"Kui Li","orcid":"0000-0002-2413-6020","position":4,"is_corresponding":false},{"id":380341,"name":"Michael H. Chen","orcid":"0000-0003-4273-5817","position":5,"is_corresponding":false},{"id":435461,"name":"Runhua Liu","orcid":"0000-0002-0892-6946","position":6,"is_corresponding":false},{"id":435462,"name":"Lizhong Wang","orcid":"0000-0003-1980-4730","position":7,"is_corresponding":false},{"id":528469,"name":"Xue‐Long Sun","orcid":"0000-0001-6483-1709","position":8,"is_corresponding":false},{"id":436705,"name":"Guo‐Yun Chen","orcid":null,"position":9,"is_corresponding":false},{"id":435460,"name":"Darong Yang","orcid":"0000-0002-5343-9047","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:32:32.651796Z","pmid":null,"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":[]}