Molecular basis of receptor binding and antibody neutralization of Omicron

The SARS-CoV-2 Omicron displays hanging immune evasion and is spreading quickly worldwide. Understanding the structural foundation of the excessive transmissibility and enhanced immune evasion of Omicron is of excessive significance. Right here by way of cryo-EM evaluation, we current each the closed and open states of the Omicron spike (S), which seem extra compact than the counterparts of the G614 pressure1, doubtlessly associated to Omicron residue substitutions-induced enhanced inter-protomer and S1-S2 interactions. The closed state displaying dominant inhabitants could point out a conformational masking mechanism for Omicron’s immune evasion. Furthermore, we seize three states for the Omicron S-ACE2 advanced, revealing that the substitutions on the Omicron RBM lead to new salt bridges/H-bonds, extra favorable electrostatic floor properties, and general strengthened S-ACE2 interplay, consistent with the noticed greater ACE2 affinity of Omicron S relative to G614. Moreover, we decide constructions of Omicron S in advanced with the Fab of S3H3, an antibody in a position to cross-neutralize main variants of concern together with Omicron, elucidating the structural foundation for S3H3-mediated broad-spectrum neutralization. Our findings shed new lights on the receptor engagement and antibody neutralization/evasion of Omicron and can also inform design of broadly efficient SARS-CoV-2 vaccines.

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