{"doi":"10.3390/biom15111489","title":"Structural Insights into the SARS-CoV-2 Spike Protein and Its Implications for Antibody Resistance","abstract":"The COVID-19 pandemic, caused by SARS-CoV-2, has profoundly affected global health and the economy. The emergence of variants with spike mutations, particularly within the receptor-binding domain (RBD), has reduced the efficacy of many neutralizing antibodies (nAbs), and recent variants, including KP.3 and other circulating strains, show partial escape from infection- or vaccine-induced immunity. To overcome this, developing broad-spectrum nAbs that target the conserved S2 subunit of the spike protein is crucial. Unlike the highly mutable RBD, the S2 region remains structurally conserved, providing a promising foundation for universal protection. Deeper insight into S2 structure and function, together with advances in bispecific antibody design, could facilitate the development of next-generation therapeutics resilient to viral evolution. This review examines the structural evolution of the SARS-CoV-2 spike, focusing on the therapeutic potential of S2-targeting antibodies and strategies to overcome antibody resistance.","journal":"Biomolecules","year":2025,"id":524714,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":988275,"name":"Kohji Noguchi","orcid":"0000-0002-9080-0807","position":1,"is_corresponding":false},{"id":988270,"name":"Yuichiro Yamamoto","orcid":"0000-0003-1992-1806","position":0,"is_corresponding":true}],"reference_count":113,"raw_metadata":null,"created_at":"2026-07-19T02:50:16.562292Z","pmid":"41301407","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":[]}