{"doi":"10.1016/j.jbc.2025.108319","title":"Isolation and structure elucidation of Dm-CVNH, a new cyanovirin-N homolog with activity against SARS-CoV-2 and HIV-1","abstract":"An anti-HIV screen of natural product extracts resulted in the discovery of a new antiviral protein through bioassay-guided fractionation of an aqueous extract of the ascidian Didemnum molle . The protein was sequenced through a combination of tandem mass spectroscopy and N-terminal Edman degradation of peptide fragments after a series of endoproteinase digestions. The primary amino acid sequence and disulfide bonding pattern of the 102-amino acid protein were closely related to the antiviral protein cyanovirin-N (CV-N). This new CV-N homolog was named Dm -CVNH. Alphafold2 prediction resulted in a tertiary structure, highly similar to CV-N, comprised of two symmetrically related domains that contained five β-strands and two α-helical turns each. Dm -CVNH showed specificity for high mannose and oligomannose structures, bound to HIV-1 gp-120 and potently inactivated HIV in neutralization assays (EC 50 of 0.95 nM). Dm -CVNH inhibited infection in a SARS-CoV-2 live virus assays and was shown to bind to the S1 domain of SARS-CoV-2 Spike glycoprotein. Dm -CVNH behaved in a manner similar to CV-N, binding with a 2:1 stoichiometry to Spike (both to WH-1 and Omicron variants) and preferring the Omicron variant (Kd 42 nM) to original WH-1 (Kd = 89 nM) Spike. This sensitivity to emergent strains was mirrored in viral neutralization assays where Dm -CVNH potently inhibited the infection of Omicron strains XBB.1.16 and JN.1 (IC 50 = 11–18 nM).","journal":"Journal of Biological Chemistry","year":2025,"id":562082,"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":0.9303,"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":344998,"name":"Lauren R. H. Krumpe","orcid":"0000-0001-9463-9777","position":1,"is_corresponding":false},{"id":974186,"name":"Shilpa R. Shenoy","orcid":null,"position":2,"is_corresponding":false},{"id":528309,"name":"Jennifer A. Wilson","orcid":"0000-0002-2381-1338","position":3,"is_corresponding":false},{"id":372791,"name":"Tad Guszczynski","orcid":null,"position":4,"is_corresponding":false},{"id":257550,"name":"Curtis J. Henrich","orcid":"0000-0002-5940-6553","position":5,"is_corresponding":false},{"id":915580,"name":"J. Sebastian Temme","orcid":"0000-0001-8306-2810","position":6,"is_corresponding":false},{"id":519329,"name":"Jeffrey C. Gildersleeve","orcid":"0000-0002-3744-6423","position":7,"is_corresponding":false},{"id":1464517,"name":"Elisa Molina-Molina","orcid":null,"position":8,"is_corresponding":false},{"id":653887,"name":"Itziar Erkizia","orcid":"0000-0003-1244-8972","position":9,"is_corresponding":false},{"id":97916,"name":"Julià Blanco","orcid":"0000-0002-2225-0217","position":10,"is_corresponding":false},{"id":312203,"name":"Nuria Izquierdo‐Useros","orcid":"0000-0002-1039-1821","position":11,"is_corresponding":false},{"id":554441,"name":"Fábio Luís Lima Monteiro","orcid":"0000-0002-9107-6865","position":12,"is_corresponding":false},{"id":36913,"name":"Amílcar Tanuri","orcid":"0000-0003-0570-750X","position":13,"is_corresponding":false},{"id":527437,"name":"Elíbio Rech","orcid":"0000-0001-8588-0673","position":14,"is_corresponding":false},{"id":257552,"name":"Barry R. O’Keefe","orcid":"0000-0003-0772-4856","position":15,"is_corresponding":false},{"id":1093561,"name":"Maria Orfanoudaki","orcid":"0000-0002-9409-7645","position":0,"is_corresponding":true}],"reference_count":108,"raw_metadata":null,"created_at":"2026-07-19T02:56:01.883848Z","pmid":"39956341","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":[]}