The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines. Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope in the receptor-binding domain of SARS-CoV-2 spike that is well conserved and show that these Abs can neutralize several variants of concerns.
【저자키워드】 antibodies, SARS-CoV-2, viral infection, X-ray crystallography, 【초록키워드】 COVID-19, public health, Mutation, Vaccines, Neutralizing antibodies, antibody, COVID-19 pandemic, Antibody therapeutics, Epitopes, Viral, Receptor-binding domain, SARS-CoV-2 variants, cross-neutralizing antibody, RBD, virus variants, crystal structure, epitope, affinity, SARS-CoV-2 spike, sarbecovirus, N-terminal domain, isolates, crystal structures, causative agent, domain, several variants, global efforts, viral spike, circulating SARS-CoV-2 variants, variants of SARS-CoV-2, neutralize, conserved, recognize, the RBD, the receptor-binding domain, disrupt, global effort, several variant, 【제목키워드】 antibody, circulating variant,