{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:36:58Z","timestamp":1780555018901,"version":"3.54.1"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2022YFB3207200"],"award-info":[{"award-number":["2022YFB3207200"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82111530302"],"award-info":[{"award-number":["82111530302"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20200109144201725"],"award-info":[{"award-number":["JCYJ20200109144201725"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Exploration"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ongoing mutations of the SARS\u2010CoV\u20102 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT\u2010CoV144 is reported, which exhibits broad neutralizing activity against SARS\u2010CoV\u20102 by inducing the conformation of spike trimer dimers. IBT\u2010CoV144 was isolated from an immunized alpaca using the RBD of wild\u2010type SARS\u2010CoV\u20102, and it showed strong cross\u2010reactive binding and neutralizing potency against diverse SARS\u2010CoV\u20102 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT\u2010CoV144 confers fantastic protective efficacy against the challenge of Omicron BA.1 variant in BALB\/c mice model. The structure analysis of the complex between spike (S) protein, conducted using Cryo\u2010EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the \u201cup\u201d state and bound by six VHHs. IBT\u2010CoV144 binds to the lateral region of the RBD on the S protein, facilitating the aggregation of S proteins. This aggregation results in steric hindrance, which disrupts the recognition of the virus by ACE2 on host cells. The discovery of IBT\u2010CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next\u2010generation vaccines.<\/jats:p>","DOI":"10.1002\/exp.20230086","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T18:51:13Z","timestamp":1702666273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A novel nanobody broadly neutralizes SARS\u2010CoV\u20102 via induction of spike trimer dimers conformation"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-4459","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for infectious disease Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Research Center Yuebei People's Hospital, Shantou University Medical College Shaoguan China"},{"name":"Shenzhen Immunity Biotech Co., Ltd. Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease National Clinical Researcher Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for infectious disease Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-3750","authenticated-orcid":false,"given":"Chenguang","family":"Shen","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong) Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health Department of Laboratory Medicine Zhujiang Hospital Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Song","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for infectious disease Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease National Clinical Researcher Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Peng","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for infectious disease Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Gong","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for infectious disease Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Dai","sequence":"additional","affiliation":[{"name":"Health and Quarantine Laboratory Guangzhou Customs District Technology Centre  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongwei","family":"Xie","sequence":"additional","affiliation":[{"name":"Medical Research Center Yuebei People's Hospital, Shantou University Medical College Shaoguan China"},{"name":"Shenzhen Immunity Biotech Co., Ltd. Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana Aleksandrovna","family":"Khrustaleva","sequence":"additional","affiliation":[{"name":"Multidisciplinary Diagnostic Laboratory Institute of Physiology of the National Academy of Sciences of Belarus  Minsk Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav Victorovich","family":"Khrustalev","sequence":"additional","affiliation":[{"name":"Multidisciplinary Diagnostic Laboratory Institute of Physiology of the National Academy of Sciences of Belarus  Minsk Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongting","family":"Huo","sequence":"additional","affiliation":[{"name":"Guangdong Fapon Biopharma Inc.  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangdong Fapon Biopharma Inc.  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincun","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease National Clinical Researcher Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxia","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for infectious disease Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhou","family":"Lu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Clinical Research Center for infectious disease Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00996-y"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00672-y"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01249-8"},{"key":"e_1_2_8_2_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01562-w"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc2241"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00495-3"},{"key":"e_1_2_8_3_3","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28106"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00672-y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.04.023"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04385-3"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04388-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-063011-092449"},{"key":"e_1_2_8_8_1","first-page":"521","volume":"614","author":"Cao Y.","year":"2023","journal-title":"Nature"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27610-z"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00684-0"},{"key":"e_1_2_8_10_1","volume":"3","author":"Yang Z.","year":"2022","journal-title":"Innovation"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.03.009"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.11.057"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114726"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2153"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115401"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.15.5938"}],"container-title":["Exploration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/EXP.20230086","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T04:52:51Z","timestamp":1718859171000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/EXP.20230086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/EXP.20230086"],"URL":"https:\/\/doi.org\/10.1002\/exp.20230086","archive":["Portico"],"relation":{},"ISSN":["2766-8509","2766-2098"],"issn-type":[{"value":"2766-8509","type":"print"},{"value":"2766-2098","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]},"assertion":[{"value":"2023-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"20230086"}}