Author:
Sun Dapeng,Sang Zhe,Kim Yong Joon,Xiang Yufei,Cohen Tomer,Belford Anna K.,Huet Alexis,Conway James F.,Sun Ji,Taylor Derek J.,Schneidman-Duhovny Dina,Zhang Cheng,Huang Wei,Shi Yi
Abstract
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 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
26 articles.
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