Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.
Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of ... concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.
Mesh Terms:
Animals, Antibodies, Neutralizing, Antibodies, Viral, Broadly Neutralizing Antibodies, Cryoelectron Microscopy, Epitopes, Mice, Severe acute respiratory syndrome-related coronavirus
Animals, Antibodies, Neutralizing, Antibodies, Viral, Broadly Neutralizing Antibodies, Cryoelectron Microscopy, Epitopes, Mice, Severe acute respiratory syndrome-related coronavirus
Cell Rep
Date: Jan. 23, 2024
PubMed ID: 38175758
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