{"doi":"10.1021/acsnanoscienceau.5c00090","title":"Recombinant Protein Nanoparticles for Dual-Stage Inhibition of SARS-CoV-2 Infection","abstract":"High Resolution Image Download MS PowerPoint Slide Recombinant proteins exhibit significant promise as antiviral therapeutics. Here, we present a nanotherapeutic platform that, owing to its unique ability to self-assemble, can present multiple functionalities at the liquid–liquid interface. We genetically modified the sequence of an amphiphilic plant-derived protein called oleosin to induce spontaneous self-assembly into micellar nanoparticles. Using SARS-CoV-2 as a model, we demonstrate the potential of a recombinant protein nanoparticle to inhibit two different stages of viral infection. Oleosin variants were engineered to present miniproteins 1) that block the SARS-CoV-2 spike protein binding with human ACE2 receptors and 2) that inhibit virus-cell membrane fusion. Micellar nanoparticles assembled from these proteins are multivalent and bifunctional and achieved potent inhibition of the virus with an IC 50 of less than 8 nM, which was more than an order of magnitude lower than that from monofunctional particles. This strategy demonstrates a promising path for developing a single protein nanoparticle capable of inhibition of multiple stages of a viral infection using solely recombinant techniques.","journal":"ACS Nanoscience Au","year":2025,"id":586520,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9443,"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":287173,"name":"Hsiang-chi Tseng","orcid":null,"position":1,"is_corresponding":false},{"id":1501481,"name":"Kerolos Agayby","orcid":null,"position":2,"is_corresponding":false},{"id":553733,"name":"Abby Odle","orcid":"0000-0003-0526-9503","position":3,"is_corresponding":false},{"id":231180,"name":"Daniel A. Hammer","orcid":"0000-0002-3522-3154","position":4,"is_corresponding":false},{"id":107099,"name":"Ricardo Rajsbaum","orcid":"0000-0002-5058-5444","position":5,"is_corresponding":false},{"id":405113,"name":"Rajarshi Chattaraj","orcid":"0000-0002-2641-6974","position":6,"is_corresponding":false},{"id":1501480,"name":"Giang H. Pham","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:59:32.191237Z","pmid":"42004263","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":[]}