{"doi":"10.1002/advs.202513710","title":"DNA Nanostructure‐Templated Multivalency Enables Broad‐Spectrum Virus Inhibition","abstract":"The rapid evolution and antigenic diversity of influenza A viruses (IAVs) continue to challenge antiviral strategies, highlighting the need for broadly effective and modular therapeutic platforms. While single-domain nanobodies and DNA aptamer-based inhibitors have emerged as promising candidates, their efficacy is limited by monomeric binding to the hemagglutinin (HA) proteins populating the viral envelope. A programmable antiviral platform based on a honeycomb-shaped designer DNA nanostructure (HC-DDN) engineered to multivalently display HA-targeting ligands with nanometer precision is presented. Two constructs are synthesized, HC-Nanobody and HC-Aptamer, organized in trimeric clusters to match the native HA trimer geometry. Using murine-adapted H1N1 and H3N2 models, it is shown that both constructs outperform their free counterparts in viral neutralization and cytoprotection. HC-Nanobody construct achieves >99% inhibition of viral entry and improves cell viability by 35-45% at nanomolar concentrations. To assess translational relevance, the HC-Nanobody construct in a porcine IAV infection model is further evaluated, where it maintains high antiviral efficacy (>97% inhibition) and confers a 30-55% increase in cell viability relative to free nanobodies, confirming robust cross-species performance. Overall, this work demonstrates the power of geometry-matched multivalency to enhance viral neutralization and provides a rational blueprint for designing broad-spectrum antivirals against rapidly evolving respiratory pathogens.","journal":"Advanced Science","year":2025,"id":529383,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9427,"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":660227,"name":"Abhisek Dwivedy","orcid":"0000-0001-9745-8138","position":1,"is_corresponding":false},{"id":1034354,"name":"Dhanush Gandavadi","orcid":"0009-0000-3063-4408","position":2,"is_corresponding":false},{"id":1080003,"name":"Chi Chen","orcid":"0009-0004-3662-0006","position":3,"is_corresponding":false},{"id":430525,"name":"Lifeng Zhou","orcid":"0000-0001-5479-3681","position":4,"is_corresponding":false},{"id":1408176,"name":"Jinwei Duan","orcid":"0000-0002-2821-8904","position":5,"is_corresponding":false},{"id":1408177,"name":"Mareddy Vineetha Reddy","orcid":"0000-0002-0026-866X","position":6,"is_corresponding":false},{"id":552361,"name":"Yīng Fāng","orcid":"0000-0002-3289-3654","position":7,"is_corresponding":false},{"id":411072,"name":"Xing Wang","orcid":"0000-0001-9930-3287","position":8,"is_corresponding":false},{"id":1045447,"name":"Saurabh Umrao","orcid":"0000-0002-9735-8062","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:50:56.971987Z","pmid":"41270218","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":[]}