{"doi":"10.1073/pnas.2312755121","title":"Identification and characterization of a nonbiological small-molecular mimic of a Zika virus conformational neutralizing epitope","abstract":"Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools and effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library of 508,032 synthetic, non-natural oligomers, we selected and characterized small molecules that mimic ZIKV epitopes. High-throughput fluorescence-activated cell sorter-based bead screening was used to select molecules that bound IgG from ZIKV-immune but not from dengue-immune sera. Deep sequencing of the DNA from the \"Zika-only\" beads identified 40 candidate molecular structures. A lead candidate small molecule \"CZV1-1\" was selected that correctly identifies serum specimens from Zika-experienced patients with good sensitivity and specificity (85.3% and 98.4%, respectively). Binding competition studies of purified anti-CZV1-1 IgG against known ZIKV-specific monoclonal antibodies (mAbs) showed that CZV1-1 mimics a nonlinear, neutralizing conformational epitope in the domain III of the ZIKV envelope. Purified anti-CZV1-1 IgG neutralized infection of ZIKV in cell cultures with potencies comparable to highly specific ZIKV-neutralizing mAbs. This study demonstrates an innovative approach for identification of synthetic non-natural molecular mimics of conformational virus epitopes. Such molecular mimics may have value in the development of accurate diagnostic assays for Zika, as well as for other viruses.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":442437,"datarank":0.4324666305641106,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.08707886661500368,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.08707886661500368,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1255880,"name":"Patrick J. McEnaney","orcid":"0009-0001-1659-2034","position":1,"is_corresponding":false},{"id":1255881,"name":"Yongseok Park","orcid":"0000-0002-2058-6833","position":2,"is_corresponding":false},{"id":1256213,"name":"Anthea L. Bouwer","orcid":null,"position":3,"is_corresponding":false},{"id":1255882,"name":"Elton José Ferreira Chaves","orcid":"0000-0001-8573-2216","position":4,"is_corresponding":false},{"id":1255883,"name":"Roberto D. Lins","orcid":"0000-0002-3983-8025","position":5,"is_corresponding":false},{"id":393281,"name":"Nicholas G. Paciaroni","orcid":"0000-0001-5799-1544","position":6,"is_corresponding":false},{"id":420702,"name":"Paige Dickson","orcid":"0000-0002-9196-2031","position":7,"is_corresponding":false},{"id":717268,"name":"Graham J. Carlson","orcid":null,"position":8,"is_corresponding":false},{"id":271998,"name":"Marli Tenório Cordeiro","orcid":"0000-0001-8196-807X","position":9,"is_corresponding":false},{"id":441629,"name":"Tereza Magalhães","orcid":"0000-0003-1474-0889","position":10,"is_corresponding":false},{"id":1256214,"name":"Jodi K. Craigo","orcid":null,"position":11,"is_corresponding":false},{"id":441635,"name":"Ernesto T. A. Marques","orcid":"0000-0003-3826-9358","position":12,"is_corresponding":false},{"id":145257,"name":"Thomas Kodadek","orcid":"0000-0003-1930-4795","position":13,"is_corresponding":false},{"id":107137,"name":"Donald S. Burke","orcid":null,"position":14,"is_corresponding":false},{"id":441632,"name":"Priscila M. S. Castanha","orcid":"0000-0002-1220-5308","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:15.932178Z","pmid":"38743628","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":[]}