Broad‐Spectrum Engineered Multivalent Nanobodies Against SARS‐CoV‐1/2

Abstract: SARS‐CoV‐2 Omicron sublineages escape most preclinical/clinical neutralizing antibodies in development, suggesting that previously employed antibody screening strategies are not well suited to counteract the rapid mutation of SARS‐CoV‐2. Therefore, there is an urgent need to screen better broad‐spectrum neutralizing antibody. In this study, a comprehensive approach to design broad‐spectrum inhibitors against both SARS‐CoV‐1 and SARS‐CoV‐2 by leveraging the structural diversity of nanobodies is proposed. This includes the de novo design of a fully human nanobody library and the camel immunization‐based nanobody library, both targeting conserved epitopes, as well as the development of multivalent nanobodies that bind nonoverlapping epitopes. The results show that trivale B11‐E8‐F3, three nanobodies joined tandemly in trivalent form, have the broadest spectrum and efficient neutralization activity, which spans from SARS‐CoV‐1 to SARS‐CoV‐2 variants. It is also demonstrated that B11‐E8‐F3 has a very prominent preventive and some therapeutic effect in animal models of three authentic viruses. Therefore, B11‐E8‐F3 has an outstanding advantage in preventing SARS‐CoV‐1/SARS‐CoV‐2 infections, especially in immunocompromised populations or elderly people with high‐risk comorbidities.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Broad‐Spectrum Engineered Multivalent Nanobodies Against SARS‐CoV‐1/2 ; day:07 ; month:10 ; year:2024 ; extent:18
Advanced science ; (07.10.2024) (gesamt 18)

Urheber
Wang, Zhihong
Shi, Zhuangzhuang
Liao, Xiaochen
Quan, Guiqi
Dong, Hui
Zhao, Pinnan
Zhou, Yangyihua
Shi, Ning
Wang, Jie
Wu, Yahui
Qiao, Chunxia
Li, Xin ying
Zhang, Ran
Wang, Zekun
Wang, Tiecheng
Gao, Xiang
Feng, Jiannan
Luo, Longlong

DOI
10.1002/advs.202402975
URN
urn:nbn:de:101:1-2410081407160.056271788029
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:27 MESZ

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Beteiligte

  • Wang, Zhihong
  • Shi, Zhuangzhuang
  • Liao, Xiaochen
  • Quan, Guiqi
  • Dong, Hui
  • Zhao, Pinnan
  • Zhou, Yangyihua
  • Shi, Ning
  • Wang, Jie
  • Wu, Yahui
  • Qiao, Chunxia
  • Li, Xin ying
  • Zhang, Ran
  • Wang, Zekun
  • Wang, Tiecheng
  • Gao, Xiang
  • Feng, Jiannan
  • Luo, Longlong

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