{"doi":"10.1101/2025.09.21.677611","title":"Broad-Spectrum HIV-1 Detection and Neutralization via Multivalent Designer DNA Nanostructures","abstract":"Abstract Early and accurate detection of HIV-1 remains a critical unmet need, particularly during the acute phase of infection when viral loads are low and transmission risk is highest. Here, we report a modular diagnostic and antiviral platform based on designer DNA nanostructures engineered for high-affinity recognition of the HIV-1 envelope glycoprotein (GP120). A custom DNA aptamer, termed HINT, was developed to bind GP120 across major HIV-1 subtypes (Groups M and P; subtypes A and B) with nanomolar affinity. To amplify binding strength, HINT aptamers were spatially patterned onto a net-shaped DNA nanostructure (DNA-Net HINT ) that geometrically matches the trimeric GP120 spikes on the viral surface. Using multivalent interactions, the nanostructure enabled up to 10 4 -fold improvement in binding affinity (sub-picomolar K D ), confirmed by surface plasmon resonance. Integration of DNA-Net HINT into a paper-based lateral flow assay produced a low-cost, saliva-compatible self-testing device capable of detecting intact HIV-1 virions at concentrations as low as 328 viral copies per test, outperforming commercial fourth-generation rapid diagnostic tests. In addition to its diagnostic capabilities, the DNA-Net HINT construct exhibited potent antiviral activity, reducing pseudovirus infection with an EC 50 of ∼1.8 nM, nearly 1,000-fold more effective than free aptamers. This work demonstrates a dual-function DNA nanotechnology platform that enables both ultrasensitive HIV-1 detection and entry inhibition. The approach is broadly applicable to other enveloped viruses and represents a promising step toward next-generation molecular theranostics for infectious disease management.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559112,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9525,"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":1208527,"name":"Mengxi Zheng","orcid":"0000-0002-1625-6663","position":2,"is_corresponding":false},{"id":299724,"name":"Varada Anirudhan","orcid":"0000-0002-5370-1092","position":3,"is_corresponding":false},{"id":1021529,"name":"Uğur Parlatan","orcid":"0000-0001-7106-5993","position":4,"is_corresponding":false},{"id":239686,"name":"Timothy J. Henrich","orcid":"0000-0002-6684-0622","position":5,"is_corresponding":false},{"id":228721,"name":"Brian T. Cunningham","orcid":"0000-0002-9681-2104","position":6,"is_corresponding":false},{"id":228637,"name":"Utkan Demirci","orcid":"0000-0003-2784-1590","position":7,"is_corresponding":false},{"id":1459839,"name":"Lijun Rong","orcid":"0000-0001-7171-2839","position":8,"is_corresponding":false},{"id":411072,"name":"Xing Wang","orcid":"0000-0001-9930-3287","position":9,"is_corresponding":false},{"id":1045447,"name":"Saurabh Umrao","orcid":"0000-0002-9735-8062","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:30.312295Z","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":[]}