In the comparatively short time since then, it has achieved pandemic status, causing more than 13.3 million cases, leading to more than 600,000 deaths. SARS-CoV-2 was first identified as the etiologic agent of the novel pneumonia COVID-19, in late 2019. Ty1 is therefore an excellent candidate as an intervention against COVID-19. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the ‘up’ and ‘down’ conformations, sterically hindering RBD-ACE2 binding.
Ty1 binds the RBD with high affinity, occluding ACE2. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor.
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