Figure 1. Approach.

(A) Schematic of our strategy for generating, identifying and characterizing large, diverse repertoires of nanobodies that bind the Spike protein of CoV-2. The highest quality nanobodies were assayed for their ability to neutralize CoV-2 pseudo-virus, CoV-2 virus and viral entry into primary human airway epithelial cells. We also measured the activities of homodimers/homotrimers and mixtures. (B) A network visualization of 374 high confidence CDR3 sequences identified from Mass Spectrometry workflow. Nodes (CDR3 sequences) were connected by edges defined by a Damerau-Levenshtein distance of no more than 3, forming 183 isolated components. A thicker edge indicates a smaller distance value, i.e. a closer relation. (C) Dendrogram showing sequence relationships between the 113 selected nanobodies, demonstrating that the repertoire generally retains significant diversity in both anti-S1 (green) and anti-S2 (blue) nanobodies, albeit with a few closely related members. Scale, 0.2 substitutions per residue.