دورية أكاديمية

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, Yang, Zhang, Junfang, Zhang, Shengnan, Zhang, Chenhui, Shen, Chenguang, Song, Shuo, Wang, Yanqun, Peng, Yun, Gong, Xiaohua, Dai, Jun, Xie, Chongwei, Khrustaleva, Tatyana Aleksandrovna, Khrustalev, Vladislav Victorovich, Huo, Yongting, Lu, Di, Yao, Da, Zhao, Jincun, Liu, Yingxia, Lu, Hongzhou
المصدر: Exploration (Beijing) ; ISSN:2766-2098 ; Volume:4 ; Issue:3
بيانات النشر: PubMed Central
سنة النشر: 2024
المجموعة: PubMed Central (PMC)
مصطلحات موضوعية: SARS‐CoV‐2, broad neutralizing, inhalable administration, nanobody, spike trimer dimers
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: https://doi.org/10.1002/EXP.20230086Test; https://pubmed.ncbi.nlm.nih.gov/38939869Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189563Test/
DOI: 10.1002/EXP.20230086
الإتاحة: https://doi.org/10.1002/EXP.20230086Test
https://pubmed.ncbi.nlm.nih.gov/38939869Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189563Test/
حقوق: © 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.
رقم الانضمام: edsbas.C0430E88
قاعدة البيانات: BASE