دورية أكاديمية
أعرض في EDS

A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation.

التفاصيل البيبلوغرافية
العنوان: A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation.
المؤلفون: Yang Y; 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., Zhang J; Medical Research Center Yuebei People's Hospital, Shantou University Medical College Shaoguan China.; Shenzhen Immunity Biotech Co., Ltd. Shenzhen China., Zhang S; 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., Zhang C; 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., Shen C; BSL-3 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., Song S; 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., Wang Y; 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., Peng Y; 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., Gong X; 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., Dai J; Health and Quarantine Laboratory Guangzhou Customs District Technology Centre Guangzhou Guangdong China., Xie C; Medical Research Center Yuebei People's Hospital, Shantou University Medical College Shaoguan China.; Shenzhen Immunity Biotech Co., Ltd. Shenzhen China., Khrustaleva TA; Multidisciplinary Diagnostic Laboratory Institute of Physiology of the National Academy of Sciences of Belarus Minsk Belarus., Khrustalev VV; Multidisciplinary Diagnostic Laboratory Institute of Physiology of the National Academy of Sciences of Belarus Minsk Belarus., Huo Y; Guangdong Fapon Biopharma Inc. Shenzhen China., Lu D; Guangdong Fapon Biopharma Inc. Shenzhen China., Yao D; Department of Thoracic Surgery The First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital Shenzhen Guangdong China., Zhao J; 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., Liu Y; 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., Lu H; 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.
المصدر: Exploration (Beijing, China) [Exploration (Beijing)] 2023 Dec 15; Vol. 4 (3), pp. 20230086. Date of Electronic Publication: 2023 Dec 15 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Inc., Wiley Beijing Office in partnership with Henan University and Chinese Association of Nanobiology Country of Publication: China NLM ID: 9918383883006676 Publication Model: eCollection Cited Medium: Internet ISSN: 2766-2098 (Electronic) Linking ISSN: 27662098 NLM ISO Abbreviation: Exploration (Beijing) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Beijing : John Wiley & Sons Inc., Wiley Beijing Office in partnership with Henan University and Chinese Association of Nanobiology, [2021]-
مستخلص: The ongoing mutations of the SARS-CoV-2 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-CoV144 is reported, which exhibits broad neutralizing activity against SARS-CoV-2 by inducing the conformation of spike trimer dimers. IBT-CoV144 was isolated from an immunized alpaca using the RBD of wild-type SARS-CoV-2, and it showed strong cross-reactive binding and neutralizing potency against diverse SARS-CoV-2 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT-CoV144 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-EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the "up" state and bound by six VHHs. IBT-CoV144 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-CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next-generation vaccines.
Competing Interests: The authors declare no conflicts of interest.
(© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)
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فهرسة مساهمة: Keywords: SARS‐CoV‐2; broad neutralizing; inhalable administration; nanobody; spike trimer dimers
تواريخ الأحداث: Date Created: 20240628 Latest Revision: 20240629
رمز التحديث: 20240629
مُعرف محوري في PubMed: PMC11189563
DOI: 10.1002/EXP.20230086
PMID: 38939869
قاعدة البيانات: MEDLINE
الوصف
تدمد:2766-2098
DOI:10.1002/EXP.20230086