Identification of a nanobody able to catalyze the destruction of the spike-trimer of SARS-CoV-2.
10.1007/s11684-025-1128-4
- Author:
Kai WANG
1
;
Duanfang CAO
2
;
Lanlan LIU
1
;
Xiaoyi FAN
2
;
Yihuan LIN
1
;
Wenting HE
2
;
Yunze ZHAI
3
;
Pingyong XU
2
;
Xiyun YAN
2
;
Haikun WANG
4
;
Xinzheng ZHANG
5
;
Pengyuan YANG
6
Author Information
1. Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
3. State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
4. State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. hkwang@tongji.edu.cn.
5. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. xzzhang@ibp.ac.cn.
6. Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. pyyang@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
SARS-CoV-2;
catalyzation;
nanobody;
rapid destruction;
spike-trimer
- MeSH:
Single-Domain Antibodies/immunology*;
Spike Glycoprotein, Coronavirus/metabolism*;
SARS-CoV-2/immunology*;
Animals;
Humans;
Antibodies, Neutralizing/immunology*;
Camelus;
COVID-19/immunology*;
Antibodies, Viral/immunology*;
Angiotensin-Converting Enzyme 2
- From:
Frontiers of Medicine
2025;19(3):493-506
- CountryChina
- Language:English
-
Abstract:
Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
