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TitlePotent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes.
Journal, issue, pagesbioRxiv, Year 2021
Publish dateMar 10, 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 AbstractThere is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel ...There is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel aerosolization route to treat SARS-CoV-2 infections efficiently. However, it remains unknown if they possess broadly neutralizing activities against the prevalent circulating strains. We found that potent neutralizing Nbs are highly resistant to the convergent variants of concern that evade a large panel of neutralizing antibodies (Abs) and significantly reduce the activities of convalescent or vaccine-elicited sera. Subsequent determination of 9 high-resolution structures involving 6 potent neutralizing Nbs by cryoelectron microscopy reveals conserved and novel epitopes on virus spike inaccessible to Abs. Systematic structural comparison of neutralizing Abs and Nbs provides critical insights into how Nbs uniquely target the spike to achieve high-affinity and broadly neutralizing activity against the evolving virus. Our study will inform the rational design of novel pan-coronavirus vaccines and therapeutics.
External linksbioRxiv / PubMed:33758850 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 3.8 Å
Structure data

24253

7n9a

EMDB-24253, PDB-7n9a:
Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes-CovS RBD with NB21
Method: EM (single particle) / Resolution: 3.5 Å

24255

7n9b

EMDB-24255: SARS-CoV-2 S with NB21 nanobody
PDB-7n9b: Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes-CovS with NB21
Method: EM (single particle) / Resolution: 3.8 Å

24256

7n9c

EMDB-24256, PDB-7n9c:
Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes-CovS with NB95
Method: EM (single particle) / Resolution: 3.71 Å

24257

7n9e

EMDB-24257, PDB-7n9e:
Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes-CovS with NB34
Method: EM (single particle) / Resolution: 3.52 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • lama glama (llama)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / CovS NB21 nanobody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / CovS NB34 nanobody

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