RT Journal Article
SR Electronic
T1 SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.19.473380
DO 10.1101/2021.12.19.473380
A1 Dhiraj Mannar
A1 James W. Saville
A1 Xing Zhu
A1 Shanti S. Srivastava
A1 Alison M. Berezuk
A1 Katharine S. Tuttle
A1 Citlali Marquez
A1 Inna Sekirov
A1 Sriram Subramaniam
YR 2021
UL http://biorxiv.org/content/early/2021/12/21/2021.12.19.473380.abstract
AB The newly reported Omicron variant is poised to replace Delta as the most rapidly spread SARS-CoV-2 variant across the world. Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2. These interactions appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, explaining our finding of similar biochemical ACE2 binding affinities for Delta and Omicron variants. Neutralization assays show that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion, with greater evasion observed in sera obtained from unvaccinated convalescent patients as compared to doubly vaccinated individuals (8-vs 3-fold). The retention of strong interactions at the ACE2 interface and the increase in antibody evasion are molecular factors that likely contribute to the increased transmissibility of the Omicron variant.Competing Interest StatementAll authors except for S.S. declare no competing interests. S.S. is the Founder and CEO of Gandeeva Therapeutics Inc.