SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein-ACE2 complex

The newly reported Omicron variant is poised to replace Delta as the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant across the world. Cryo-electron microscopy (cryo-EM) structural analysis of the Omicron variant spike protein in complex with human angioten-sinconverting enzyme 2 (ACE2) reveals new salt bridges and hydrogen bonds formed by mutated residues arginine-493, serine-496, and arginine-498 in the receptor binding domain with ACE2. These interactions appear to compensate for other Omicron mutations such as the substitution of asparagine for lysine at position 417 (K417N) that are known to reduce ACE2 binding affinity, resulting in similar biochemical ACE2 binding affinities for the Delta and Omicron variants. Neutralization assays show that pseudoviruses that display the Omicron spike protein exhibit increased antibody evasion. The increase in antibody evasion and the retention of strong interactions at the ACE2 interface thus represent important molecular features that likely contribute to the rapid spread of the Omicron variant.

Automated summary

The newly reported Omicron variant shows new salt bridges and hydrogen bonds formed by mutated residues in the receptor binding domain, compensating for reduced ACE2 binding affinity. It also exhibits increased antibody evasion, which likely contributes to its rapid spread.