The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

Brian D Quinlan; Huihui Mou; Lizhou Zhang; Yan Gao; Wenhui He; Amrita Ojha; Mark S Parcells; Guangxiang Luo; Wenhui Li; Guocai Zhong; Hyeryun Choe; Michael Farzan

The receptor-binding domains (RBDs, also described as S B ) of SARS-CoV-1 and SARS-CoV-2 directly bind ACE2 ( Figure 1C ) (Li et al., 2005; Walls et al., 2020; Wong et al., 2004; Wrapp et al., 2020) . These RBDs are structurally and functionally distinct from the remainder of the S1 domain, and express and fold as independent domains (Wong et al., 2004) . Both RBDs are highly stable and held together by four disulfide bonds. Structural studies of the SARS-CoV-2 RBD bound to ACE2 have identified a variable region, termed the receptor-binding motif (RBM), which directly engages ACE2 (Li et al., 2005) . This region is divergent between SARS-CoV-1 and SARS-CoV-2 ( Figure 1D ) although both RBD bind ACE2 in the same orientation and rely on conserved, mostly aromatic, residues to engage this receptor. The divergence between the SARS-CoV-1 and SARS-CoV-2 RBM domains suggest that this region is subject to ongoing positive selection from the humoral response in various hosts. Despite this divergence, some antibodies, notably CR3022, bind both RBD domains (Tian et al., 2020) .