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

Yang, Yang1; Zhang, Junfang2,6; Zhang, Shengnan3; Zhang, Chenhui1; Shen, Chenguang4; Song, Shuo1; Wang, Yanqun3; Peng, Yun1; Gong, Xiaohua1; Dai, Jun5; Xie, Chongwei2,6; Khrustaleva, Tatyana Aleksandrovna7; Khrustalev, Vladislav Victorovich7; Huo, Yongting8; Lu, Di8; Yao, Da9; Zhao, Jincun3; Liu, Yingxia1; Lu, Hongzhou1

2024-06-01

10.1002/EXP.20230086

EXPLORATION   影响因子和分区

2766-8509

2766-2098

["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.","This study describes a novel nanobody that could induce the trimer dimers conformation of the Spike protein to neutralize the SARS-CoV-2 infection. This nanobody exhibits a broad neutralizing spectrum against various SARS-CoV-2 variants and has the potential to be administered through inhalation. image"]

broad neutralizing inhalable administration nanobody SARS-CoV-2 spike trimer dimers

ESCI

英语

第一 ; 通讯

National Natural Science Foundation of China[82111530302] ; Guangdong Basic and Applied Research Projects[2022B1515020075] ; Shenzhen Science and Technology Innovation Commission[JCYJ20200109144201725] ; Shenzhen High-level Hospital Construction Fund[23250G1001] ; Medical Research Foundation of Guangdong Province[B2022270] ; null[2022YFB3207200]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Multidisciplinary Sciences

WOS:001250767700010

WILEY

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Shenzhen Clin Res Ctr Infect Dis, Shenzhen Key Lab Pathogen & Immun,Hosp 2, Shenzhen, Peoples R China
2.Shantou Univ, Yuebei Peoples Hosp, Med Coll, Med Res Ctr, Shaoguan, Peoples R China
3.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Researcher Ctr Resp Dis, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
4.Southern Med Univ, Sch Publ Hlth, Lab Guangdong BSL 3, Guangdong Prov Key Lab Trop Dis Res,Dept Lab Med,Z, Guangzhou, Peoples R China
5.Guangzhou Customs Dist Technol Ctr, Hlth & Quarantine Lab, Guangzhou, Guangdong, Peoples R China
6.Shenzhen Biocup Biotech Co Ltd, Shenzhen 518000, Peoples R China
7.Natl Acad Sci Belarus, Multidisciplinary Diagnost Lab, Inst Physiol, Minsk, BELARUS
8.BGI Shenzhen, Shenzhen, Peoples R China
9.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Dept Gastroenterol, Shenzhen 518028, Guangdong, Peoples R China

Yang, Yang,Zhang, Junfang,Zhang, Shengnan,et al. A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation[J]. EXPLORATION,2024,4(3).

Yang, Yang.,Zhang, Junfang.,Zhang, Shengnan.,Zhang, Chenhui.,Shen, Chenguang.,...&Lu, Hongzhou.(2024).A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation.EXPLORATION,4(3).

Yang, Yang,et al."A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation".EXPLORATION 4.3(2024).