Super broad and protective nanobodies against Sarbecoviruses including SARS-CoV-1 and the divergent SARS-CoV-2 subvariant KP.3.1.1
The ongoing evolution and immune escape of SARS-CoV-2, alongside the potential threat of SARS-CoV-1 and other sarbecoviruses, underscore the urgent need for effective strategies against their infection and transmission. This study highlights the discovery of nanobodies from immunized alpacas, which demonstrate exceptionally broad and potent neutralizing capabilities against the recently emerged and more divergent SARS-CoV-2 Omicron subvariants including JD.1.1, JN.1, KP.3, KP.3.1.1, as well as SARS-CoV-1 and coronaviruses from bats and pangolins utilizing receptor ACE2. Among these, Tnb04-1 emerges as the most broad and potent, binding to a conserved hydrophobic pocket in the spike's receptor-binding domain, distinct from the ACE2 binding site. This interaction disrupts the formation of a proteinase K-resistant core, crucial for viral-cell fusion. Notably, intranasal administration of Tnb04-1 in Syrian hamsters effectively prevented respiratory infection and transmission of the authentic Omicron XBB.1.5 subvariant. Thus, Thb04-1 holds promise in combating respiratory acquisition and transmission of diverse sarbecoviruses.
Authors
- Ziqing Yang (ORCID: https://orcid.org/0000-0002-0492-0862)
- Linqi Zhang (ORCID: https://orcid.org/0000-0003-4931-509X)
- Mingxi Li
- Yan Liang (ORCID: https://orcid.org/0000-0002-8536-5951)
- Runhong Zhou (ORCID: https://orcid.org/0000-0001-6642-6029)
- Mengyue Niu (ORCID: https://orcid.org/0000-0002-9714-593X)
- Jing Wei (ORCID: https://orcid.org/0000-0003-1062-6691)
- Yufan Yang (ORCID: https://orcid.org/0000-0001-6148-8570)
- Sisi Shan (ORCID: https://orcid.org/0000-0002-7184-6818)
- Zimeng Wei (ORCID: https://orcid.org/0000-0002-6534-3982)
- Haodi Dong (ORCID: https://orcid.org/0000-0002-8119-2598)
- Kun Zhu (ORCID: https://orcid.org/0000-0002-8723-7574)
- Xinquan Wang (ORCID: https://orcid.org/0000-0003-3136-8070)
- Yuyang Zeng (ORCID: https://orcid.org/0000-0003-0593-4542)
- Na Liu (ORCID: https://orcid.org/0000-0002-3274-5416)
- Qi Zhang (ORCID: https://orcid.org/0000-0002-8144-3609)
- Qianqian Yang (ORCID: https://orcid.org/0000-0002-4331-5059)
- Jing Chen (ORCID: https://orcid.org/0000-0001-5972-3623)
- Yuting Chen (ORCID: https://orcid.org/0000-0003-4661-2048)
- Zhiwei Chen (ORCID: https://orcid.org/0009-0004-7626-3787)
- Qile Guo
- Yuhan Wu (ORCID: https://orcid.org/0009-0002-1282-814X)
- Xuanling Shi (ORCID: https://orcid.org/0000-0001-8418-9661)
- Isabella Yunfei Zeng
- Han Wang (ORCID: https://orcid.org/0009-0008-1462-649X)
Institutions
- Hong Kong Science and Technology Parks Corporation (HK)
- Shenzhen Bay Laboratory (CN)
- Tsinghua–Berkeley Shenzhen Institute (CN)
- Massachusetts Institute of Technology (US)
- University of Hong Kong (HK)
- Tsinghua University (CN)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1371/journal.ppat.1012625
- Citations
- 4
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.56
Funders
- National Natural Science Foundation of China
- Innovation and Technology Commission
- Tsinghua University
- Health and Medical Research Fund