Summary Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses. Graphical abstract Highlights • X-ray and EM structures of CV38-142 with SARS-CoV-2 and SARS-CoV RBDs and spikes • N343 glycan and bound waters facilitate cross-reactivity to SARS-related viruses • CV38-142 synergizes with CR3022 conserved site antibodies, in particular COVA1-16 • These two cross-neutralizing antibodies neutralize SARS-CoV-2 variants of concern Antibody CV38-142 from a COVID-19 patient cross-reacts with SARS-related viruses. Liu et al. reveal that CV38-142 interacts with the S309 N343 glycan site and synergizes with COVA1-16 that binds the conserved CR3022 site. Combination of the two cross-neutralizing antibodies shows enhanced neutralization to circulating variants of concern B.1.1.7 and B.1.351.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, Crystallography, antibody cocktail, cross-neutralizing antibody, synergy, antibody-antigen interaction, 3D structure, 【초록키워드】 coronavirus disease, viruses, Structure, antibodies, Coronavirus disease 2019, Vaccine, Neutralizing antibodies, spike, antibody, SARS-CoV, B.1.351, neutralization, threat, SARS-CoV-2 variant, Epidemics, cross-reactivity, X-ray, SARS-CoV-2 variants, B.1.1.7, zoonotic, therapeutic, Effectiveness, Pandemics, crystal structure, information, glycan, Sarbecoviruses, antigenic drift, Interaction, antigenic variation, COVID-19 patient, therapeutic antibodies, CR3022, crystal structures, S309, bound waters, Recognition, Threats, Abstract, these viruses, spikes, related viruses, complex, antigenic, SARS-related coronaviruses, receptor-binding domains, SARS-CoV RBD, circulating variants, cross-neutralizing antibodies, COVA1-16, SARS-CoV RBDs, SARS-related viruses, neutralize, ENhance, bind, glycosylation site, PROTECT, shown, caused, conserved, SARS-related virus, facilitate, provide, interact, the receptor-binding domain, cross-react, circulating variant, cross-neutralizing, 【제목키워드】 Infection, Combination, Prevent, SARS-CoV pseudovirus,