Figure 1. Design strategy.
(a) Trimeric HA bound to receptor analog 6‧SLN (PDB entry 4wea). (b) Broadly neutralizing antibody loops interact with the receptor binding site either by inserting an aromatic or aliphatic residue into a pocket above the conserved Trp153, as for HCDR3 of C055 and many other RBS-targeted antibodies8 or by using an aspartate to mimic the carboxyl of sialic acid6, 7 (Fig.S1). (c) Evaluation of 80 HA binder designs by yeast display followed by next-generation sequencing. The design pool was screened against H3 HK68 and two negative control targets (Ebola GP and E. coli intimin) to monitor off-target binding to HA. Enrichment values are the ratio of the frequency of a given design in FACS-selected populations for one of the three targets to the frequency in the original unselected population. A number of the designs specifically bind HA, but not Ebola GP or intimin. (d) Models of designs that specifically bind HA (#24 and HSB); the C05 derived loop is colored in purple.
