Fig. 4: Spike binding comparison of differentially oriented trimeric ACE2 antagonists.
From: Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist
(i) Cartoon representations of SARS-CoV-2 spike protein (blue) and trimeric antagonists. a, b Construct protein expression for a trimerization domain (blue open triangle) and linker (light blue curves/cones) fused to the N-terminus of ACE2 extracellular domain (ACE2; pink cartoon with RBD binding site highlighted teal), or b ACE2 fused via C-terminal linker (orange curves/cones) to trimerization domain (red open triangle). (ii–iv) Simulated binding of three equivalents of trimeric ACE2 antagonists to three spike proteins with each having (ii) one, (iii) two, or (iv) three RBD domains in the ‘open’/ACE2-binding conformation. ACE2-bound RBDs are highlighted in green, and in red with circles when not bound/exposed. Unbound ACE2 monomers are depicted with pink cartoons and cones demonstrating the flexibility of linker domains. The N- and C-termini of bound ACE2 monomers are shown as red and blue circles, respectively. Created with Biorender.com.
