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

1/20/2022 11:45:00 PM

Structural analysis of the Omicron spike protein reveals how, despite having many mutations, it binds to ACE2 w/ an affinity similar to Delta. It also shows increased antibody evasion. These factors likely contribute to Omicron’s increased transmissibility

The large number of mutations on the surface of the spike protein including the immunodominant RBD (Fig. 1) would be expected to help the virus escape antibodies elicited by vaccination or prior infection. It is interesting that the Omicron variant evolved to retain its ability to bind ACE2 efficiently despite these extensive mutations. The cryo-EM structure of the spike protein-ACE2 complex provides a structural rationale for how this is achieved: interactions involving the new mutations in the Omicron variant at residues 493, 496, 498, and 501 appear to restore ACE2 binding efficiency that would be lost due to other mutations such as K417N. The Omicron variant thus appears to have evolved to selectively balance an increase in escape from neutralization with its ability to interact efficiently with ACE2. The increase in antibody evasion and the retention of strong interactions at the ACE2 interface are thus factors that likely contribute to the increase in transmissibility of the Omicron variant.

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Fourth Vaccine Shot Less Effective Against Omicron, Israeli Study SaysA fourth shot of the COVID-19 vaccine boosts antibodies but doesn’t provide enough protection to prevent infections from the Omicron variant, according to new research at an Israeli hospital. ach12sha So, why on earth is all these “shots” and “jabs” about if they’re not actually “protecting and preventing” COVID-19 infections, be it any of the variants? Maybe 5th shot will do!

Study shows how SARS-CoV-2 Omicron evades our immune response and remains infective ImmuneResponse Omicron SARSCoV2 Coronavirus COVID UBC CDCofBC

Is a universal coronavirus vaccine on the horizon?Scientists are racing to develop a single vaccine that protects against many SARS-CoV-2 variants, as well as emerging coronaviruses with the potential to trigger a new pandemic. Please, kill me already. You just lost my respect and my follow. What you are posting is pure bullship. Never thought of National Geographic as a goat but this is proof. Now do the story on how in Europe we're seeing negative efficacy of the vaccinated against Omicron.

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Sputnik V shows higher Omicron-antibody levels than Pfizer in preliminary studyA small preliminary laboratory study has shown that levels of Omicron-neutralising antibodies of people vaccinated with Russia's Sputnik V vaccine did not decline as much as of those who had Pfizer shots. Pity Russians don’t take Sputnik V, supplies to other countries came short, certification stalled due to unreliable data, it was used as a propaganda tool. Sputnik V has been a total failure. The study was paíd by Putin Fake

Vaccine Apartheid Means Pandemic 'Nowhere Near Over': WHO Chief\u0022With the incredible growth of Omicron globally, new variants are likely to emerge,\u0022 warned WHO Director-General Tedros Adhanom Ghebreyesus.

) supporting the finding that the Omicron variant is more resistant to neutralization dependent on prior infection with an earlier variant or vaccination than any other variant of concern that has emerged over the course of the COVID-19 pandemic. The large number of mutations on the surface of the spike protein including the immunodominant RBD ( Fig. 1 ) would be expected to help the virus escape antibodies elicited by vaccination or prior infection. It is interesting that the Omicron variant evolved to retain its ability to bind ACE2 efficiently despite these extensive mutations. The cryo-EM structure of the spike protein-ACE2 complex provides a structural rationale for how this is achieved: interactions involving the new mutations in the Omicron variant at residues 493, 496, 498, and 501 appear to restore ACE2 binding efficiency that would be lost due to other mutations such as K417N. The Omicron variant thus appears to have evolved to selectively balance an increase in escape from neutralization with its ability to interact efficiently with ACE2. The increase in antibody evasion and the retention of strong interactions at the ACE2 interface are thus factors that likely contribute to the increase in transmissibility of the Omicron variant. Acknowledgments We thank Dr. Karoline Leopold (UBC) and Dr. Charles Leung (Gandeeva Therapeutics Inc.) for assistance with the surface plasmon resonance experiments and for helpful discussions. Funding: This work was supported by awards to S.S. from a Canada Excellence Research Chair Award, the VGH Foundation, Genome BC, Canada, and from the Tai Hung Fai Charitable Foundation. D.M. is supported by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship Master's Award (CGS-M). J.W.S is supported by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (CGS D) and a UBC President's Academic Excellence Initiative PhD Award. Author contributions: This work was the result of a concerted team effort from all individuals listed as authors. J.W.S. and D.M., carried out expression and purification of the Omicron spike protein and antibodies. D.M. performed the SPR binding analyses. D.M. and J.W.S. performed the pseudovirus neutralization experiments. I.S. and C.M. provided the vaccine-induced patient-derived sera samples and aided the interpretation of the patient data. A.M.B., S.S.S. and K.S.T. carried out experimental aspects of electron microscopy including specimen preparation and data collection. X.Z. carried out computational aspects of image processing and structure determination. X.Z., S.S.S., D.M., J.W.S., and S.S. interpreted and analyzed the cryo-EM structures, binding analyses and patient neutralization data and composed the manuscript with input from the rest of the authors. S.S. provided overall supervision for the project. Competing interests: All authors except for S.S. declare no competing interests. S.S. is the Founder and CEO of Gandeeva Therapeutics Inc. Data and materials availability: All newly created materials described in this manuscript will be available from the corresponding author upon reasonable request. Cryo-EM reconstructions and atomic models generated during this study are available at the PDB and EMBD databases under the following accession codes: Unbound Omicron spike protein trimer (PDB ID 7T9J, EMD- EMDB 25759), global ACE2-bound Omicron spike protein trimer (PDB ID 7T9K, EMD-25760), focus-refinement of the ACE2-RBD interface for the ACE2-bound Omicron spike protein trimer (PDB ID 7T9L, EMD-25761). This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit . This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material. Supplementary Materials