Receptor binding of SARS-CoV-2 Omicron variant compared to other variants

In a recent study posted to the medRxiv* preprint server, a team of researchers compared the binding of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) Omicron’s receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor with the original Wuhan SARS-CoV-2 strain and other VOCs such as Beta and Delta.

Study: Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants. Image Credit: Teeradej/Shutterstock

The researchers also compared the ability of human sera to bind the different variants’ RBDs in patients recovering from coronavirus disease 2019 (COVID-19), individuals fully vaccinated with BNT162b2 (Corminaty) or Ad26.COV2.S (Janssen COVID-19 vaccine) vaccines and individuals who received booster vaccine doses of BNT162b2 or mRNA-1273 (Spikevax) bind the different RBDs.


In late November 2021, a new VOC named B.1.1.529 or Omicron was identified. Compared to earlier VOCs, the genomic sequences of Omicron showed significantly more amino acid (aa) mutations in its spike protein. The majority of the mutations were related to RBD. Previous studies have reported very low serum neutralizing capacity against the Omicron variant in patients recovering from COVID-19 and fully vaccinated individuals. The degree of participation of RBD mutations in Omicron variant neutralizing activity is yet to be determined.

About the study

The present study analyzed human serum samples from 27 patients recovering from COVID-19, 21 fully vaccinated individuals with either two doses of BNT162b2 vaccine or a single dose of Ad26.COV2.S vaccine, and 16 individuals who received a BNT162b2 or mRNA1273 vaccine booster dose. The researchers compared the binding potential of the ACE2 receptor of these individuals to the Omicron RBD concerning the original Wuhan strain. Further, Omicron-ACE2 binding was also compared with that of the Beta and Delta variants.

The researchers produced and extracted different RBD variants and ACE2 receptors and analyzed the binding efficiency between them in triplicates using enzyme-linked immunoassay (ELISA).


The results showed a lower binding affinity of Omicron RBD to ACE2 (EC50 150ng/mL) in comparison to the original Wuhan strain RBD (EC50 120ng/mL). However, Omicron RBD showed a higher binding affinity with ACE2 receptors than the Beta and Delta variant RBDs (EC50 89 ng/mL).

Further, the binding analysis of human sera against the Wuhan strain and Delta, Beta, and Omicron variants’ RBDs revealed significantly less binding to the Omicron RBD in patients recovering from COVID-19 and individuals fully vaccinated with the BNT162ab2 vaccine and even lesser against the Beta variant and Delta variant RBDs. Individuals vaccinated with Ad26.COV2.S vaccine displayed very low binding with all RBDs indicating the low immunogenicity of this vaccine. The booster dose group displayed almost similar binding with the Wuhan strain and the Beta and Delta variant RBDs and significantly lesser binding to Omicron RBD. There was no evidence of increased binding to the Omicron variant after a booster dose.


The RBD-ACE2 interaction is essential for SARS-CoV-2 viral entry in human hosts. According to previous studies, several Omicron RBD mutations – such as G339D, S477N, T478K, Q493K, and N501Y – were believed to increase the binding to ACE2, S371L, S373P, G446S, E484A, Q493R, and Q498R were neutral, while S375F, K417N, G496S, and Y505H were assumed to reduce the ACE2 binding.

Among the 15 aa mutations of the Omicron variant, some were similar to the mutations in other VOCs: the K417N mutation is also found in the Beta variant, the T478K mutation in the Delta variant, and the N501Y mutation in the Alpha, Beta, and Gamma variants. All these mutations might affect the ACE2 binding efficacy and immune escape. The N501Y mutation is found in approximately 90% of all sequenced Omicron variants, K417N and G446S mutations in approximately 40% of sequences, and S477N and T478K mutations in approximately 60% of the sequences.

Overall, the study results indicated reduced binding affinity of the ACE2 receptor against the Omicron RBD in sera from COVID-19 patients, fully vaccinated individuals, as well as individuals who received a booster vaccine. This suggests that current vaccinations or booster doses may be less efficient against the Omicron variant.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Schubert, M. et al. (2021) "Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants". medRxivdoi: 10.1101/2021.12.10.21267523.

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: ACE2, Amino Acid, Angiotensin, Angiotensin-Converting Enzyme 2, binding affinity, Coronavirus, Coronavirus Disease COVID-19, Efficacy, Enzyme, Genomic, Immunoassay, Mutation, Protein, Receptor, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine

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Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.

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