Cross-reaction of current available SARS-CoV-2 MAbs against the pangolin-origin coronavirus GX/P2V/2017

Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, multiple SARS-CoV-2-related viruses have been characterized, including pangolin-origin GD/1/2019 and GX/P2V/2017. Our previous study indicated that both viruses have the potential to infect humans. Here, we find that CB6 (commercial name etesevimab), a COVID-19 therapeutic monoclonal antibody (MAb) developed by our group, efficiently inhibits GD/1/2019 but not GX/P2V/2017. A total of 50 SARS-CoV-2 MAbs divided into seven groups based on their receptor-binding domain (RBD) epitopes, together with the COVID-19 convalescent sera, are systematically screened for their cross-binding and cross-neutralizing properties against GX/P2V/2017. We find that GX/P2V/2017 displays substantial immune difference from SARS-CoV-2. Furthermore, we solve two complex structures of the GX/P2V/2017 RBD with MAbs belonging to RBD-1 and RBD-5, providing a structural basis for their different antigenicity. These results highlight the necessity for broad anti-coronavirus countermeasures and shed light on potential therapeutic targets.