7ws5

Publication Abstract from PubMed

The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies.

Structures of Omicron spike complexes and implications for neutralizing antibody development.,Guo H, Gao Y, Li T, Li T, Lu Y, Zheng L, Liu Y, Yang T, Luo F, Song S, Wang W, Yang X, Nguyen HC, Zhang H, Huang A, Jin A, Yang H, Rao Z, Ji X Cell Rep. 2022 May 3;39(5):110770. doi: 10.1016/j.celrep.2022.110770. Epub 2022 , Apr 15. PMID:35477022^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.