{"doi":"10.1371/journal.ppat.1012726","title":"Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate","abstract":"Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model. Cryo-EM data revealed that Nanosota-9 neutralizes Omicron through a unique mechanism: two Nanosota-9 molecules crosslink two receptor-binding domains (RBDs) of the trimeric Omicron spike protein, preventing the RBDs from binding to the ACE2 receptor. This mechanism explains its strong anti-Omicron potency. Additionally, the Nanosota-9 binding epitopes on the spike protein are relatively conserved among Omicron subvariants, contributing to its broad anti-Omicron spectrum. Combined with our recently developed structure-guided in vitro evolution approach for nanobodies, Nanosota-9 has the potential to serve as the foundation for a superior anti-Omicron therapeutic.","journal":"PLoS Pathogens","year":2024,"id":443763,"datarank":0.3559586863616367,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.026374999761203742,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.026374999761203742,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"is_data_producer":true,"deposit_databanks":{"PDB":["9CO6","9CO7","9CO8","9CO9"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1060860,"name":"Fan Bu","orcid":"0000-0002-6965-3072","position":1,"is_corresponding":false},{"id":1258422,"name":"Divyasha Saxena","orcid":"0009-0000-3952-2066","position":2,"is_corresponding":false},{"id":1258942,"name":"Hailey Turner‐Hubbard","orcid":null,"position":3,"is_corresponding":false},{"id":1061200,"name":"Morgan Herbst","orcid":null,"position":4,"is_corresponding":false},{"id":484525,"name":"Benjamin W. Spiller","orcid":"0000-0001-5397-1028","position":5,"is_corresponding":false},{"id":866117,"name":"Brian E. Wadzinski","orcid":"0000-0002-2980-3697","position":6,"is_corresponding":false},{"id":105109,"name":"Lanying Du","orcid":"0000-0001-5955-1294","position":7,"is_corresponding":false},{"id":846345,"name":"Bin Liu","orcid":"0000-0002-6581-780X","position":8,"is_corresponding":false},{"id":817064,"name":"Jian Zheng","orcid":"0000-0003-0616-5570","position":9,"is_corresponding":false},{"id":103706,"name":"Fang Li","orcid":"0000-0002-1958-366X","position":10,"is_corresponding":false},{"id":103756,"name":"Gang Ye","orcid":"0000-0001-6034-2174","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39591462","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":[]}