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Camel nanobodies broadly neutralize SARS-CoV-2 variants
Jessica Hong1, Hyung Joon Kwon2, Raul Cachau3
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bethesda, Maryland, 20891, USA.
Biorxiv : the Preprint Server for Biology
|November 9, 2021
Summary
Two camel-derived nanobodies, 7A3 and 8A2, neutralize SARS-CoV-2 variants. Nanobody 7A3 shows therapeutic potential in mice against emerging variants.
Area of Science:
- Immunology
- Structural Biology
- Virology
Background:
- The emergence of SARS-CoV-2 variants necessitates the development of broadly neutralizing antibodies.
- Existing treatments may be less effective against new viral strains.
Approach:
- Isolation of VHH nanobodies from dromedary camel phage display libraries.
- Characterization of nanobody binding affinity and neutralization breadth against SARS-CoV-2 and its variants.
- Determination of cryo-electron microscopy (Cryo-EM) complex structures to elucidate binding mechanisms.
Key Points:
- Two nanobodies, 7A3 and 8A2, exhibit high affinity for the SARS-CoV-2 receptor-binding domain (RBD).
- Both nanobodies demonstrate broad neutralization activity against SARS-CoV-2 and its variants.
- Cryo-EM structures reveal distinct binding modes: 8A2 binds RBD in 'up' conformation, while 7A3 targets a conserved, buried site on the spike protein.
- Nanobody 7A3 provides significant protection in K18-hACE2 transgenic mice against B.1.351 and B.1.617.2 variants.
Conclusions:
- Nanobodies 7A3 and 8A2 are potent neutralizers of SARS-CoV-2 and its variants.
- Nanobody 7A3's unique binding mechanism suggests broad therapeutic potential.
- 7A3 demonstrates efficacy in a mouse model, indicating promise for controlling COVID-19 surges caused by emerging variants.
