SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex
Open accessAbstract
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 angiotensin-converting 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.
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Compared to earlier strains, Omicron has more mutation sites in the spike protein, of which 15 mutation sites are located in the receptor binding domain (RBD).
“Compared to earlier strains, Omicron has more mutation sites in the spike protein, of which 15 mutation sites are located in the receptor binding domain (RBD) [21].”
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“Compared to earlier strains, Omicron has more mutation sites in the spike protein, of which 15 mutation sites are located in the receptor binding domain (RBD) [21].”
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- Authors
- Mannar, D., Saville, J. W., Zhu, X., Srivastava, S. S., Berezuk, A. M., Tuttle, K. S., Marquez, A. C., Sekirov, I., & Subramaniam, S.
- Affiliations
- University of British Columbia (CA)
- BC Centre for Disease Control (CA)
- Corresponding author
- Mannar, Dhiraj
- Saville, James W.
- Zhu, Xing
- Subramaniam, Sriram
- ORCID
- Venue
- Science
- Published
- 2022-02-18
- Volume
- 375
- Issue
- 6582
- Pages
- 760-764
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9799367
- OpenAlex
- W4205331651
- Cited by
- 630
- References
- 39
- Citations by year
- 2026: 35 · 2025: 53 · 2024: 97 · 2023: 197 · 2022: 248
- FWCI
- 72.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- Omicron variant, spike protein, ACE2 receptor, receptor binding domain, antibody escape, salt bridges, hydrogen bonding, neutralizing antibodies, pseudovirus neutralization, Delta variant
- MeSH terms
- Protein Domains, Receptors, Coronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Monoclonal, Antibodies, Viral, Humans, Hydrogen Bonding, Models, Molecular, Mutation, Neutralization Tests, Protein Binding, Cryoelectron Microscopy, Protein Interaction Domains and Motifs, Immune Evasion, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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