{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:05:35Z","timestamp":1787994335344,"version":"build-2784847793"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2020YFA0908500"],"award-info":[{"award-number":["2020YFA0908500"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31971127"],"award-info":[{"award-number":["31971127"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801998"],"award-info":[{"award-number":["81801998"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory disease in humans. High fatality rates and continued infectiousness remain a pressing concern for global health preparedness. Antibodies targeted at the receptor-binding domain (RBD) are major countermeasures against human viral infection. Here, we report four potent nanobodies against MERS-CoV, which are isolated from alpaca, and especially the potency of Nb14 is highest in the pseudotyped virus assay. Structural studies show that Nb14 framework regions (FRs) are mainly involved in interactions targeting a novel epitope, which is entirely distinct from all previously reported antibodies, and disrupt the protein-carbohydrate interaction between residue W535 of RBD and hDPP4 N229-linked carbohydrate moiety (hDPP4-N229-glycan). Different from Nb14, Nb9 targets the cryptic face of RBD, which is distinctive from the hDPP4 binding site and the Nb14 epitope, and it induces the \u03b25-\u03b26 loop to inflect towards a shallow groove of the RBD and dampens the accommodation of a short helix of hDPP4. The particularly striking epitopes endow the two Nbs administrate synergistically in the pseudotyped MERS-CoV assays. These results not only character unprecedented epitopes for antibody recognition but also provide promising agents for prophylaxis and therapy of MERS-CoV infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012438","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T17:24:00Z","timestamp":1723656240000},"page":"e1012438","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structure defining of ultrapotent neutralizing nanobodies against MERS-CoV with novel epitopes on receptor binding domain"],"prefix":"10.1371","volume":"20","author":[{"given":"Sen","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doudou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3507-3969","authenticated-orcid":true,"given":"Yaxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"issue":"19","key":"ppat.1012438.ref001","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1056\/NEJMoa1211721","article-title":"Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia","volume":"367","author":"AM Zaki","year":"2012","journal-title":"N Engl J Med"},{"issue":"2","key":"ppat.1012438.ref002","article-title":"Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak","volume":"7","author":"Y Kim","year":"2016","journal-title":"Mbio"},{"issue":"6","key":"ppat.1012438.ref003","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.3201\/eid2506.181722","article-title":"Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015","volume":"25","author":"YS Kim","year":"2019","journal-title":"Emerg Infect Dis"},{"issue":"8","key":"ppat.1012438.ref004","doi-asserted-by":"crossref","first-page":"E217","DOI":"10.1016\/S1473-3099(18)30127-0","article-title":"Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission","volume":"18","author":"DS Hui","year":"2018","journal-title":"Lancet Infect Dis"},{"issue":"9","key":"ppat.1012438.ref005","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1080\/14760584.2020.1813574","article-title":"An overview of Middle East respiratory syndrome coronavirus vaccines in preclinical studies","volume":"19","author":"NR Zhang","year":"2020","journal-title":"Expert Rev Vaccines"},{"issue":"3","key":"ppat.1012438.ref006","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4266\/acc.2021.00388","article-title":"Comparison of characteristics and ventilatory course between coronavirus disease 2019 and Middle East respiratory syndrome patients with acute respiratory distress syndrome","volume":"36","author":"I Khalid","year":"2021","journal-title":"Acute Crit Care"},{"issue":"1","key":"ppat.1012438.ref007","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1080\/22221751.2019.1624482","article-title":"Antibodies and vaccines against Middle East respiratory syndrome coronavirus","volume":"8","author":"J Xu","year":"2019","journal-title":"Emerging Microbes & Infections"},{"issue":"3","key":"ppat.1012438.ref008","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/jobm.202000537","article-title":"SARS-CoV-2, the pandemic coronavirus: Molecular and structural insights","volume":"61","author":"SB Kadam","year":"2021","journal-title":"J Basic Microb"},{"issue":"2","key":"ppat.1012438.ref009","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S1473-3099(13)70690-X","article-title":"Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation","volume":"14","author":"BL Haagmans","year":"2014","journal-title":"Lancet Infect Dis"},{"issue":"10","key":"ppat.1012438.ref010","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S1473-3099(13)70164-6","article-title":"Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study","volume":"13","author":"CBEM Reusken","year":"2013","journal-title":"Lancet Infect Dis"},{"issue":"24","key":"ppat.1012438.ref011","article-title":"Middle East respiratory syndrome coronavirus Spike protein variants exhibit geographic differences in virulence","volume":"118","author":"LR Wong","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1012438.ref012","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"CB Jackson","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"21","key":"ppat.1012438.ref013","doi-asserted-by":"crossref","first-page":"11133","DOI":"10.1128\/JVI.00959-09","article-title":"Two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis","volume":"83","author":"S Matsuyama","year":"2009","journal-title":"J Virol"},{"issue":"10","key":"ppat.1012438.ref014","doi-asserted-by":"crossref","first-page":"5502","DOI":"10.1128\/JVI.00128-13","article-title":"The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies","volume":"87","author":"S Gierer","year":"2013","journal-title":"Journal of Virology"},{"issue":"8","key":"ppat.1012438.ref015","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/cr.2013.92","article-title":"Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4","volume":"23","author":"N Wang","year":"2013","journal-title":"Cell Res"},{"issue":"7440","key":"ppat.1012438.ref016","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature12005","article-title":"Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC","volume":"495","author":"VS Raj","year":"2013","journal-title":"Nature"},{"issue":"6965","key":"ppat.1012438.ref017","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"W Li","year":"2003","journal-title":"Nature"},{"key":"ppat.1012438.ref018","doi-asserted-by":"crossref","first-page":"15092","DOI":"10.1038\/ncomms15092","article-title":"Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains","volume":"8","author":"Y Yuan","year":"2017","journal-title":"Nat Commun"},{"issue":"10","key":"ppat.1012438.ref019","article-title":"Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation","volume":"8","author":"ZH Qian","year":"2013","journal-title":"Plos One"},{"issue":"35","key":"ppat.1012438.ref020","doi-asserted-by":"crossref","first-page":"E7348","DOI":"10.1073\/pnas.1707304114","article-title":"Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen","volume":"114","author":"J Pallesen","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"33","key":"ppat.1012438.ref021","doi-asserted-by":"crossref","first-page":"10473","DOI":"10.1073\/pnas.1510199112","article-title":"Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus","volume":"112","author":"D Corti","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ppat.1012438.ref022","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/cr.2015.113","article-title":"A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein","volume":"25","author":"Y Li","year":"2015","journal-title":"Cell Res"},{"key":"ppat.1012438.ref023","doi-asserted-by":"crossref","first-page":"13133","DOI":"10.1038\/srep13133","article-title":"Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27","volume":"5","author":"X Yu","year":"2015","journal-title":"Sci Rep"},{"issue":"10","key":"ppat.1012438.ref024","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02002-17","article-title":"Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape","volume":"92","author":"L Wang","year":"2018","journal-title":"J Virol"},{"issue":"2","key":"ppat.1012438.ref025","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.celrep.2018.06.041","article-title":"Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein","volume":"24","author":"S Zhang","year":"2018","journal-title":"Cell Rep"},{"issue":"1","key":"ppat.1012438.ref026","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1038\/s41467-019-10897-4","article-title":"Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein","volume":"10","author":"H Zhou","year":"2019","journal-title":"Nat Commun"},{"issue":"301","key":"ppat.1012438.ref027","doi-asserted-by":"crossref","first-page":"301ra132","DOI":"10.1126\/scitranslmed.aac7462","article-title":"A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates","volume":"7","author":"K Muthumani","year":"2015","journal-title":"Sci Transl Med"},{"key":"ppat.1012438.ref028","doi-asserted-by":"crossref","first-page":"7712","DOI":"10.1038\/ncomms8712","article-title":"Evaluation of candidate vaccine approaches for MERS-CoV","volume":"6","author":"L Wang","year":"2015","journal-title":"Nat Commun"},{"key":"ppat.1012438.ref029","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41541-017-0029-1","article-title":"Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model","volume":"2","author":"VJ Munster","year":"2017","journal-title":"NPJ Vaccines"},{"issue":"30","key":"ppat.1012438.ref030","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1016\/j.vaccine.2017.05.032","article-title":"ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice","volume":"35","author":"NK Alharbi","year":"2017","journal-title":"Vaccine"},{"issue":"6268","key":"ppat.1012438.ref031","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.aad1283","article-title":"An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels","volume":"351","author":"BL Haagmans","year":"2016","journal-title":"Science"},{"issue":"3","key":"ppat.1012438.ref032","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00430-009-0116-7","article-title":"Single domain antibodies: promising experimental and therapeutic tools in infection and immunity","volume":"198","author":"J Wesolowski","year":"2009","journal-title":"Med Microbiol Immun"},{"issue":"4","key":"ppat.1012438.ref033","article-title":"Nanobody-A versatile tool for cancer diagnosis and therapeutics","volume":"13","author":"MM Liu","year":"2021","journal-title":"Wires Nanomed Nanobi"},{"issue":"11","key":"ppat.1012438.ref034","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1080\/17474086.2020.1819230","article-title":"A critical evaluation of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura","volume":"13","author":"I Gomez-Segui","year":"2020","journal-title":"Expert Rev Hematol"},{"key":"ppat.1012438.ref035","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-animal-021419-083831","article-title":"Applications of Nanobodies","volume":"9","author":"S. Muyldermans","year":"2021","journal-title":"Annu Rev Anim Biosci"},{"key":"ppat.1012438.ref036","doi-asserted-by":"crossref","first-page":"105265","DOI":"10.1016\/j.antiviral.2022.105265","article-title":"A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy","volume":"199","author":"Y Wang","year":"2022","journal-title":"Antiviral Res"},{"issue":"8","key":"ppat.1012438.ref037","article-title":"Development of a Bispecific Nanobody Targeting CD20 on B-Cell Lymphoma Cells and CD3 on T Cells","volume":"10","author":"Y Liu","year":"2022","journal-title":"Vaccines (Basel)"},{"issue":"18","key":"ppat.1012438.ref038","doi-asserted-by":"crossref","first-page":"e2201433119","DOI":"10.1073\/pnas.2201433119","article-title":"Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants","volume":"119","author":"J Hong","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"ppat.1012438.ref039","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.cell.2020.05.047","article-title":"Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies","volume":"181","author":"D Wrapp","year":"2020","journal-title":"Cell"},{"issue":"621","key":"ppat.1012438.ref040","doi-asserted-by":"crossref","first-page":"eabi7826","DOI":"10.1126\/scitranslmed.abi7826","article-title":"An affinity-enhanced, broadly neutralizing heavy chain-only antibody protects against SARS-CoV-2 infection in animal models","volume":"13","author":"B Schepens","year":"2021","journal-title":"Sci Transl Med"},{"issue":"1","key":"ppat.1012438.ref041","doi-asserted-by":"crossref","first-page":"4420","DOI":"10.1038\/s41467-020-18174-5","article-title":"An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction","volume":"11","author":"L Hanke","year":"2020","journal-title":"Nat Commun"},{"issue":"6530","key":"ppat.1012438.ref042","doi-asserted-by":"crossref","DOI":"10.1126\/science.abe6230","article-title":"Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape","volume":"371","author":"PA Koenig","year":"2021","journal-title":"Science"},{"issue":"18","key":"ppat.1012438.ref043","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00837-18","article-title":"A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV","volume":"92","author":"G Zhao","year":"2018","journal-title":"J Virol"},{"issue":"8","key":"ppat.1012438.ref044","doi-asserted-by":"crossref","first-page":"eaas9667","DOI":"10.1126\/sciadv.aas9667","article-title":"Chimeric camel\/human heavy-chain antibodies protect against MERS-CoV infection","volume":"4","author":"V Stalin Raj","year":"2018","journal-title":"Sci Adv"},{"issue":"3","key":"ppat.1012438.ref045","article-title":"A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration","volume":"37","author":"XL Wu","year":"2021","journal-title":"Cell Reports"},{"key":"ppat.1012438.ref046","article-title":"Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22)","volume":"13","author":"XL Wu","year":"2022","journal-title":"Frontiers in Immunology"},{"issue":"40","key":"ppat.1012438.ref047","first-page":"E8508","article-title":"Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein","volume":"114","author":"W Li","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"ppat.1012438.ref048","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/s41594-019-0334-7","article-title":"Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors","volume":"26","author":"YJ Park","year":"2019","journal-title":"Nat Struct Mol Biol"},{"issue":"7","key":"ppat.1012438.ref049","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/prot.25497","article-title":"Comparative analysis of nanobody sequence and structure data","volume":"86","author":"LS Mitchell","year":"2018","journal-title":"Proteins"},{"issue":"1","key":"ppat.1012438.ref050","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01062-13","article-title":"Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus","volume":"5","author":"M Cotten","year":"2014","journal-title":"mBio"},{"issue":"3","key":"ppat.1012438.ref051","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.chom.2014.08.009","article-title":"Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26","volume":"16","author":"Q Wang","year":"2014","journal-title":"Cell Host Microbe"},{"issue":"8","key":"ppat.1012438.ref052","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1128\/JVI.03445-14","article-title":"Glycosylation of Mouse DPP4 Plays a Role in Inhibiting Middle East Respiratory Syndrome Coronavirus Infection","volume":"89","author":"KM Peck","year":"2015","journal-title":"Journal of Virology"},{"issue":"Pt 8","key":"ppat.1012438.ref053","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1107\/S0907444906019949","article-title":"HKL-3000: the integration of data reduction and structure solution\u2014from diffraction images to an initial model in minutes","volume":"62","author":"W Minor","year":"2006","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 11","key":"ppat.1012438.ref054","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1107\/S0907444902016657","article-title":"PHENIX: building new software for automated crystallographic structure determination","volume":"58","author":"PD Adams","year":"2002","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 12","key":"ppat.1012438.ref055","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"P Emsley","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 1","key":"ppat.1012438.ref056","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1107\/S0907444907047580","article-title":"ARP\/wARP and molecular replacement: the next generation","volume":"64","author":"SX Cohen","year":"2008","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1012438.ref057","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/1743-422X-10-266","article-title":"A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV","volume":"10","author":"G Zhao","year":"2013","journal-title":"Virol J"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T17:24:39Z","timestamp":1723656279000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012438"}},"subtitle":[],"editor":[{"given":"Julie","family":"Overbaugh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,14]]},"references-count":57,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012438","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,14]]}}}