Molecular basis of receptor binding and antibody neutralization of Omicron


The SARS-CoV-2 Omicron reveals 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 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 complicated, revealing that the substitutions on the Omicron RBM end in new salt bridges/H-bonds, extra favorable electrostatic floor properties, and total strengthened S-ACE2 interplay, in step with the noticed larger ACE2 affinity of Omicron S relative to G614. Moreover, we decide constructions of Omicron S in complicated with the Fab of S3H3, an antibody capable of 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 might also inform design of broadly efficient SARS-CoV-2 vaccines.

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