Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer

Abstract

The emergence of the Omicron strain of SARS-CoV-2 caused higher immune escape, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. In this study, we identified a SARS-CoV-2 neutralizing antibody, 553-49, which neutralizes all variants by targeting a completely conserved novel epitope. In addition, we revealed that IgG 553-15 neutralizes SARS-CoV-2 by cross-linking virions and that 553-60 functions by blocking receptor binding. Comparison of different receptor binding domain (RBD) epitopes revealed that the 553-49 epitope is hidden in the S trimer and keeps a high degree of conservation during SARS-CoV-2 evolution, making 553-49 a promising therapeutic reagent against the emerging Omicron and future variants of SARS-CoV-2.