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Title | An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 4420, Year 2020 |
Publish date | Sep 4, 2020 |
Authors | Leo Hanke / Laura Vidakovics Perez / Daniel J Sheward / Hrishikesh Das / Tim Schulte / Ainhoa Moliner-Morro / Martin Corcoran / Adnane Achour / Gunilla B Karlsson Hedestam / B Martin Hällberg / Ben Murrell / Gerald M McInerney / |
PubMed Abstract | SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive ...SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Ty1 binds the RBD with high affinity, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the 'up' and 'down' conformations, sterically hindering RBD-ACE2 binding. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19. |
External links | Nat Commun / PubMed:32887876 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.93 Å |
Structure data | EMDB-11526, PDB-6zxn: EMDB-11728: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / spike protein / neutralising antibody |