{"doi":"10.1002/adtp.202100099","title":"Engineered Multivalent Nanobodies Potently and Broadly Neutralize SARS‐CoV‐2 Variants","abstract":"The COVID-19 pandemic continues to be a severe threat to human health, especially due to current and emerging SARS-CoV-2 variants with potential to escape humoral immunity developed after vaccination or infection. The development of broadly neutralizing antibodies that engage evolutionarily conserved epitopes on coronavirus spike proteins represents a promising strategy to improve therapy and prophylaxis against SARS-CoV-2 and variants thereof. Herein, a facile multivalent engineering approach is employed to achieve large synergistic improvements in the neutralizing activity of a SARS-CoV-2 cross-reactive nanobody (VHH-72) initially generated against SARS-CoV. This synergy is epitope specific and is not observed for a second high-affinity nanobody against a non-conserved epitope in the receptor-binding domain. Importantly, a hexavalent VHH-72 nanobody retains binding to spike proteins from multiple highly transmissible SARS-CoV-2 variants (B.1.1.7 and B.1.351) and potently neutralizes them. Multivalent VHH-72 nanobodies also display drug-like biophysical properties, including high stability, high solubility, and low levels of non-specific binding. The unique neutralizing and biophysical properties of VHH-72 multivalent nanobodies make them attractive as therapeutics against SARS-CoV-2 variants.","journal":"Advanced Therapeutics","year":2021,"id":162935,"datarank":1.3346239039198227,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.7636245304542746,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.7636245304542746,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":37,"citers_with_citation_signal":34,"citers_with_endowment":34,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"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":657371,"name":"John S. Schardt","orcid":"0000-0002-5605-4732","position":1,"is_corresponding":false},{"id":657370,"name":"Alec A. Desai","orcid":"0000-0002-8322-7096","position":2,"is_corresponding":false},{"id":58843,"name":"Emily K. Makowski","orcid":"0000-0002-9709-9873","position":3,"is_corresponding":false},{"id":241630,"name":"Matthew D. Smith","orcid":"0000-0001-6614-569X","position":4,"is_corresponding":false},{"id":657372,"name":"Ghasidit Pornnoppadol","orcid":"0000-0002-0474-2031","position":5,"is_corresponding":false},{"id":657373,"name":"Mayara Garcia de Mattos Barbosa","orcid":"0000-0002-1861-5762","position":6,"is_corresponding":false},{"id":329029,"name":"Marília Cascalho","orcid":"0000-0002-2695-3921","position":7,"is_corresponding":false},{"id":527076,"name":"Thomas M. Lanigan","orcid":"0009-0008-1741-6682","position":8,"is_corresponding":false},{"id":657375,"name":"Peter M. Tessier","orcid":"0000-0002-3220-007X","position":9,"is_corresponding":false},{"id":657939,"name":"Jennifer M. Zupancic","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:17.971865Z","pmid":"34514086","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":[]}