{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:45:01Z","timestamp":1776919501873,"version":"3.51.2"},"reference-count":54,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Support Foundation of the Federal District","award":["FAPDF 00193.0000.1054\/2021-79"],"award-info":[{"award-number":["FAPDF 00193.0000.1054\/2021-79"]}]},{"name":"Research Support Foundation of the Federal District","award":["CAPES 88887.513930\/2020-00"],"award-info":[{"award-number":["CAPES 88887.513930\/2020-00"]}]},{"name":"Research Support Foundation of the Federal District","award":["CNPq"],"award-info":[{"award-number":["CNPq"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel","award":["FAPDF 00193.0000.1054\/2021-79"],"award-info":[{"award-number":["FAPDF 00193.0000.1054\/2021-79"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel","award":["CAPES 88887.513930\/2020-00"],"award-info":[{"award-number":["CAPES 88887.513930\/2020-00"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel","award":["CNPq"],"award-info":[{"award-number":["CNPq"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["FAPDF 00193.0000.1054\/2021-79"],"award-info":[{"award-number":["FAPDF 00193.0000.1054\/2021-79"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["CAPES 88887.513930\/2020-00"],"award-info":[{"award-number":["CAPES 88887.513930\/2020-00"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["CNPq"],"award-info":[{"award-number":["CNPq"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zika virus infections exhibit recurrent outbreaks and can be responsible for disease complications such as congenital Zika virus syndrome. Effective therapeutic interventions are still a challenge. Antibodies can provide significant protection, although the antibody response may fail due to antibody-dependent enhancement reactions. The choice of the target antigen is a crucial part of the process to generate effective neutralizing antibodies. Human anti-Zika virus antibodies were selected by phage display technology. The antibodies were selected against a mimetic peptide based on the fusion loop region in the protein E of Zika virus, which is highly conserved among different flaviviruses. Four rounds of selection were performed using the synthetic peptide in two strategies: the first was using the acidic elution of bound phages, and the second was by applying a competing procedure. After panning, the selected VH and VL domains were determined by combining NGS and bioinformatic approaches. Three different human monoclonal antibodies were expressed as scFvs and further characterized. All showed a binding capacity to Zika (ZIKV) and showed cross-recognition with yellow fever (YFV) and dengue (DENV) viruses. Two of these antibodies, AZ1p and AZ6m, could neutralize the ZIKV infection in vitro. Due to the conservation of the fusion loop region, these new antibodies can potentially be used in therapeutic intervention against Zika virus and other flavivirus illnesses.<\/jats:p>","DOI":"10.3390\/ijms23147805","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T22:57:06Z","timestamp":1658098626000},"page":"7805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["New Anti-Flavivirus Fusion Loop Human Antibodies with Zika Virus-Neutralizing Potential"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-0971","authenticated-orcid":false,"given":"Renato Kaylan Alves de Oliveira","family":"Fran\u00e7a","sequence":"first","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"Graduation Program in Molecular Pathology, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacyelle Medeiros","family":"Silva","sequence":"additional","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-1355","authenticated-orcid":false,"given":"Lucas Silva","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"Graduation Program in Molecular Pathology, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitri","family":"Sokolowskei","sequence":"additional","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"Graduation Program in Molecular Biology, University of Brasilia, Brasilia 70910-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-7059","authenticated-orcid":false,"given":"Marcelo Macedo","family":"Brigido","sequence":"additional","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"Graduation Program in Molecular Pathology, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"Graduation Program in Molecular Biology, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"III-Immunology Investigation Institute\u2013CNPq-MCT, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1946-7191","authenticated-orcid":false,"given":"Andrea Queiroz","family":"Maranh\u00e3o","sequence":"additional","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"Graduation Program in Molecular Pathology, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"Graduation Program in Molecular Biology, University of Brasilia, Brasilia 70910-900, Brazil"},{"name":"III-Immunology Investigation Institute\u2013CNPq-MCT, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1002\/cmdc.202000464","article-title":"Broad-Spectrum Flavivirus Inhibitors: A Medicinal Chemistry Point of View","volume":"15","author":"Felicetti","year":"2020","journal-title":"ChemMedChem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00239-020-09941-5","article-title":"Exploring Evolutionary Constraints in the Proteomes of Zika, Dengue, and Other Flaviviruses to Find Fitness-Critical Sites","volume":"88","author":"Rahaman","year":"2020","journal-title":"J. Mol. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection","volume":"353","author":"Stettler","year":"2016","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41586-018-0446-y","article-title":"The emergence of Zika virus and its new clinical syndromes","volume":"560","author":"Pierson","year":"2018","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"598","DOI":"10.2105\/AJPH.2016.303115","article-title":"Initial Description of the Presumed Congenital Zika Syndrome","volume":"106","author":"Martelli","year":"2016","journal-title":"Am. J. Public Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ebiom.2016.06.026","article-title":"Infectivity of Immature Neurons to Zika Virus: A Link to Congenital Zika Syndrome","volume":"10","author":"Hughes","year":"2016","journal-title":"eBioMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.tibs.2020.12.007","article-title":"Molecular Determinants of Flavivirus Virion Assembly","volume":"46","author":"Barnard","year":"2021","journal-title":"Trends Biochem. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41579-018-0134-9","article-title":"The evolution of Zika virus from Asia to the Americas","volume":"17","author":"Liu","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s12985-021-01611-2","article-title":"The key amino acids of E protein involved in early Flavivirus infection: Viral entry","volume":"18","author":"Hu","year":"2021","journal-title":"Virol. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Saiz, J.-C., de Oya, N.J., Bl\u00e1zquez, A.-B., Escribano-Romero, E., and Mart\u00edn-Acebes, M.A. (2018). Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus. Viruses, 10.","DOI":"10.20944\/preprints201807.0359.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e01774-21","DOI":"10.1128\/JVI.01774-21","article-title":"Structurally conserved domains between Flavivirus and alphavirus fusion glycoproteins contribute to replication and infectious virion production","volume":"96","author":"Rangel","year":"2022","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/s41564-019-0392-y","article-title":"Antibody responses to viral infections: A structural perspective across three different enveloped viruses","volume":"4","author":"Murin","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.xphs.2019.05.031","article-title":"Considerations for the Design of Antibody-Based Therapeutics","volume":"109","author":"Goulet","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1056\/NEJMoa2000226","article-title":"Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody","volume":"383","author":"Low","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41577-021-00542-x","article-title":"Neutralizing monoclonal antibodies for treatment of COVID-19","volume":"21","author":"Taylor","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1182\/bloodadvances.2021006655","article-title":"SARS-CoV-2-neutralizing antibody treatment in patients with COVID-19 and immunodeficiency due to B-cell non-Hodgkin lymphoma","volume":"6","author":"Malin","year":"2022","journal-title":"Blood Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4546","DOI":"10.1038\/s41598-019-40937-4","article-title":"An Effective Neutralizing Antibody Against Influenza Virus H1N1 from Human B Cells","volume":"9","author":"Lee","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_18","first-page":"1150","article-title":"Computational analysis of perturbations in the post-fusion Dengue virus envelope protein highlights known epitopes and conserved residues in the Zika virus","volume":"5","author":"Chakraborty","year":"2016","journal-title":"F1000Research"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.cell.2013.03.018","article-title":"Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization","volume":"153","author":"Klein","year":"2013","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.ai.2016.11.002","article-title":"Molecular Mechanisms of Somatic Hypermutation and Class Switch Recombination","volume":"133","author":"Methot","year":"2017","journal-title":"Adv. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3389\/fimmu.2020.00334","article-title":"Cross-Reactive Immunity Among Flaviviruses","volume":"11","author":"Rathore","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.cell.2017.04.024","article-title":"Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico","volume":"169","author":"Robbiani","year":"2017","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1007\/s00018-011-0872-6","article-title":"Polyreactive antibodies in adaptive immune responses to viruses","volume":"69","author":"Mouquet","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.3389\/fimmu.2019.02424","article-title":"Development of a Potent and Protective Germline-Like Antibody Lineage Against Zika Virus in a Convalescent Human","volume":"10","author":"Gao","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.cell.2020.06.044","article-title":"Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients","volume":"182","author":"Kreer","year":"2020","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.chom.2016.04.013","article-title":"Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody","volume":"19","author":"Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s41590-021-00966-6","article-title":"Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch","volume":"22","author":"Dai","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/s41467-019-09391-8","article-title":"Structure mapping of dengue and Zika viruses reveals functional long-range interactions","volume":"10","author":"Huber","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00055-16","DOI":"10.1128\/MMBR.00055-16","article-title":"The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis. Microbiol","volume":"81","author":"Heinz","year":"2017","journal-title":"Mol. Biol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Haslwanter, D., Blaas, D., Heinz, F.X., and Stiasny, K. (2017). A novel mechanism of antibody-mediated enhancement of Flavivirus infection. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006643"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Deng, Y.-Q., Dai, J.-X., Ji, G., Jiang, T., Wang, H.-J., Yang, H.-O., Tan, W.-L., Liu, R., Yu, M., and Ge, B.-X. (2011). A broadly Flavivirus cross-neutralizing monoclonal antibody that recognises a novel epitope within the fusion loop of E protein. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016059"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nature18938","article-title":"Structural basis of potent Zika-dengue virus antibody cross-neutralization","volume":"536","author":"Spaeth","year":"2016","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12987","DOI":"10.1038\/s41598-021-92403-9","article-title":"An affinity-matured human monoclonal antibody targeting fusion loop epitope of dengue virus with in vivo therapeutic potency","volume":"11","author":"Kotaki","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.chom.2018.04.004","article-title":"Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope","volume":"23","author":"Tharakaraman","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3389\/fimmu.2018.00597","article-title":"Modulation of Dengue\/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection","volume":"9","author":"Khandia","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e92428","DOI":"10.1172\/jci.insight.92428","article-title":"Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections","volume":"2","author":"Kam","year":"2017","journal-title":"JCI Insight"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1010428317695924","DOI":"10.1177\/1010428317695924","article-title":"Selection of single chain antibody fragments binding to the extracellular domain of 4-1BB receptor by phage display technology","volume":"39","author":"Bagheri","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.ijbiomac.2019.06.006","article-title":"Phage display antibody libraries: A robust approach for generation of recombinant human monoclonal antibodies","volume":"135","author":"Kumar","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1016\/j.cell.2021.11.010","article-title":"The epitope arrangement on flavivirus particles contributes to Mab C10\u2019s extraordinary neutralization breadth across Zika and dengue viruses","volume":"184","author":"Sharma","year":"2021","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cell.2017.09.002","article-title":"A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential","volume":"171","author":"Wang","year":"2017","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.immuni.2020.01.001","article-title":"Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization","volume":"52","author":"Gilchuk","year":"2020","journal-title":"Immunity"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41586-018-0531-2","article-title":"Combination therapy with anti-HIV-1 antibodies maintains viral suppression","volume":"561","author":"Mendoza","year":"2018","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7981","DOI":"10.1073\/pnas.2000414117","article-title":"A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques","volume":"117","author":"Coffey","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.celrep.2018.10.031","article-title":"A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Eescape Mutations in Non-human Primates","volume":"25","author":"Keeffe","year":"2018","journal-title":"Cell Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualisation system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_46","first-page":"126","article-title":"Construction of a human Fab phage display library from antibody repertoires of osteosarcoma patients","volume":"4","year":"2005","journal-title":"Genet. Mol. Res."},{"key":"ref_47","unstructured":"Barbas, C.F. (2001). Phage-display vectors. Phage Display: A Laboratory Manual, Cold Spring Harbor Laboratory Press."},{"key":"ref_48","first-page":"1177932220915240","article-title":"Discovering Selected Antibodies From Deep-Sequenced Phage-Display Antibody Library Using ATTILA. Bioinform","volume":"14","author":"Silva","year":"2020","journal-title":"Biol. Insights"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nprot.2016.180","article-title":"Modeling and docking of antibody structures with Rosetta","volume":"12","author":"Weitzner","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking","volume":"12","author":"Kozakov","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1093\/bioinformatics\/btr484","article-title":"COCOMAPS: A web application to analyze and visualize contacts at the interface of biomolecular complexes","volume":"27","author":"Vangone","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_52","unstructured":"Invitrogen [Internet] (2019, October 27). Champion\u2122 pET SUMO Protein Expression System manual. Roskilde (Dinamarca): Themo Fisher Scientific. Available online: https:\/\/www.thermofisher.com\/document-connect\/document-connect.html?url=https%3A%2F%2Fassets.thermofisher.com%2FTFS-Assets%2FLSG%2Fmanuals%2Fpetsumo_man.pdf."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102269","DOI":"10.1101\/pdb.prot102269","article-title":"Bradford Assay for Determining Protein Concentration","volume":"2020","author":"Kielkopf","year":"2020","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo, R.d.S., Fran\u00e7a, R., Valadares, N., Maranh\u00e3o, A., and Brigido, M. (2021). A Germline-Encoded Structural Arginine Trap Underlies the Anti-DNA Reactivity of a Murine V Gene Segment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094541"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:50:59Z","timestamp":1760140259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":54,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23147805"],"URL":"https:\/\/doi.org\/10.3390\/ijms23147805","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]}}}