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TitleA bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 155, Year 2022
Publish dateJan 10, 2022
AuthorsLeo Hanke / Hrishikesh Das / Daniel J Sheward / Laura Perez Vidakovics / Egon Urgard / Ainhoa Moliner-Morro / Changil Kim / Vivien Karl / Alec Pankow / Natalie L Smith / Bartlomiej Porebski / Oscar Fernandez-Capetillo / Erdinc Sezgin / Gabriel K Pedersen / Jonathan M Coquet / B Martin Hällberg / Ben Murrell / Gerald M McInerney /
PubMed AbstractAntibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. This emphasizes the ...Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. This emphasizes the need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we describe the isolation of a nanobody that interacts simultaneously with two RBDs from different spike trimers of SARS-CoV-2, rapidly inducing the formation of spike trimer-dimers leading to the loss of their ability to attach to the host cell receptor, ACE2. We show that this nanobody potently neutralizes SARS-CoV-2, including the beta and delta variants, and cross-neutralizes SARS-CoV. Furthermore, we demonstrate the therapeutic potential of the nanobody against SARS-CoV-2 and the beta variant in a human ACE2 transgenic mouse model. This naturally elicited bispecific monomeric nanobody establishes an uncommon strategy for potent inactivation of viral antigens and represents a promising antiviral against emerging SARS-CoV-2 variants.
External linksNat Commun / PubMed:35013189 / PubMed Central
MethodsEM (single particle)
Resolution2.89 - 3.18 Å
Structure data

12465

7nll

EMDB-12465, PDB-7nll:
SARS-CoV-2 Spike RBD (dimer) in complex with two Fu2 nanobodies
Method: EM (single particle) / Resolution: 2.89 Å

12561

7ns6

EMDB-12561, PDB-7ns6:
SARS-CoV-2 Spike (dimers) in complex with six Fu2 nanobodies
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
  • vicugna pacos (alpaca)
  • enterobacteria phage t4 (virus)
KeywordsVIRAL PROTEIN / Nanobody / Spike / Complex / Dimer

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