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TitlePotent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting diverse and conserved epitopes.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 4676, Year 2021
Publish dateAug 3, 2021
AuthorsDapeng Sun / Zhe Sang / Yong Joon Kim / Yufei Xiang / Tomer Cohen / Anna K Belford / Alexis Huet / James F Conway / Ji Sun / Derek J Taylor / Dina Schneidman-Duhovny / Cheng Zhang / Wei Huang / Yi Shi /
PubMed AbstractInterventions against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Stable and potent nanobodies (Nbs) that target the receptor binding domain (RBD) of ...Interventions against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Stable and potent nanobodies (Nbs) that target the receptor binding domain (RBD) of SARS-CoV-2 spike are promising therapeutics. However, it is unknown if Nbs broadly neutralize circulating variants. We found that RBD Nbs are highly resistant to variants of concern (VOCs). High-resolution cryoelectron microscopy determination of eight Nb-bound structures reveals multiple potent neutralizing epitopes clustered into three classes: Class I targets ACE2-binding sites and disrupts host receptor binding. Class II binds highly conserved epitopes and retains activity against VOCs and RBD. Cass III recognizes unique epitopes that are likely inaccessible to antibodies. Systematic comparisons of neutralizing antibodies and Nbs provided insights into how Nbs target the spike to achieve high-affinity and broadly neutralizing activity. Structure-function analysis of Nbs indicates a variety of antiviral mechanisms. Our study may guide the rational design of pan-coronavirus vaccines and therapeutics.
External linksNat Commun / PubMed:34344900 / PubMed Central
MethodsEM (single particle)
Resolution3.18 - 7.92 Å
Structure data

23782

7mdw

EMDB-23782, PDB-7mdw:
CryoEM structure of SARS-CoV-2 RBD in complex with nanobodies Nb21 and Nb105
Method: EM (single particle) / Resolution: 3.58 Å

23788

7me7

EMDB-23788, PDB-7me7:
CryoEM structure of SARS-CoV-2 RBD in complex with nanobodies Nb17 and Nb105
Method: EM (single particle) / Resolution: 3.73 Å

23790

7mej

EMDB-23790, PDB-7mej:
CryoEM structure of SARS-CoV-2 RBD in complex with nanobodies Nb21 and Nb36
Method: EM (single particle) / Resolution: 3.55 Å

EMDB-23802:
cryoEM map of a dimer of the trimeric SARS-CoV-2 spike in complex with Nb105
Method: EM (single particle) / Resolution: 7.92 Å

24262

7n9t

EMDB-24262, PDB-7n9t:
CryoEM structure of SARS-CoV-2 Spike in complex with Nb17
Method: EM (single particle) / Resolution: 3.18 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • lama glama (llama)
KeywordsVIRAL PROTEIN/Immune System / SARS-CoV-2 Receptor binding domain nanobody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / ANTIVIRAL PROTEIN/VIRAL PROTEIN / SARS-CoV-2 Spike Receptor binding domain nanobody / ANTIVIRAL PROTEIN / ANTIVIRAL PROTEIN-VIRAL PROTEIN complex

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