Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes [article]

Dapeng Sun, Zhe Sang, Jeff Kim, Yufei Xiang, Tomer Cohen, Anna K Belford, Alexis Huet, James F Conway, Ji Sun, Derek Taylor, Cheng Zhang, Wei Huang (+1 others)
2021 biorxiv/medrxiv  
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
more » ... 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.
doi:10.1101/2021.03.09.434592 pmid:33758850 pmcid:PMC7987009 fatcat:lcdecdjwxjbmvkrc7kzyszzupm