This study investigates the effectiveness of nanobodies (Nbs) in neutralizing circulating SARS-CoV-2 variants. Researchers found that RBD Nbs are highly resistant to variants of concern (VOCs). High-resolution cryo-electron microscopy revealed three classes of potent neutralizing epitopes: Class I targets ACE2-binding sites; Class II binds conserved epitopes; and Class III recognizes unique, antibody-inaccessible epitopes. Comparisons with neutralizing antibodies highlighted the advantages of Nbs in achieving high-affinity and broad neutralization. The study suggests potential applications in designing pan-coronavirus vaccines and therapeutics.

Dapeng 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