Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant.
PMID: 35216287
2022
International journal of molecular sciences
Result: According to the recent study, the Omicron variant can escape the neutralization of many monoclonal antibodies, where the K417N, Q493R, and E484A Omicron mutations affect the recognition of class 1 and 2 antibodies targeting the ACE2 binding epitope.
Result: For VHH E binding, the large binding affinity loss resulted from E484A, Q493R, G496S, and N501Y mutations (Figure 7C,D).
Result: Hence, multiple Omicron RBD mutations (such as Q493R, G496S, Q498R, N501Y, Y505H) may have a measurable effect on allosteric couplings i
Cross-Neutralizing Breadth and Longevity Against SARS-CoV-2 Variants After Infections.
Introduction: Finally, B.1.1.529, which was detected in Botswana on November 11, 2021 and South Africa on November 14, 2021, has 15 mutations (G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, and Y505H) in the RBD.
SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines.
Discussion: illustrated an nAb escape event by the Omicron variant, with the K417N, G446S, E484A, Q493K/R, and N440K mutations, involved in antibody escape.
Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant.
8Discussion: Hence, some bioinformatic models predicted an increase in the ACE2 binding affinity of Omicron RBD while other models rejected this scenario and stated: ""the Q493R/K mutations, in a combination with K417N and T478K, dramatically reduced the S1 RBD binding by over 100 folds""."
Method: The RBD Omicron variant was ordered as GeneString from GeneArt (Thermo Fisher) according to EPI_ISL_6590608 (partial RBD Sanger sequencing from Hong Kong), EPI_ISL_6640916, EPI_ISL_6640919, and EPI_ISL_6640917 including Q493K which was corrected later to Q493R.
Discussion: One has also to consider that we utilized in our work the originally available sequence with
Rapidly Identifying New Coronavirus Mutations of Potential Concern in the Omicron Variant Using an Unsupervised Learning Strategy.
Abstract: To build an investigative framework, we have applied an unsupervised machine learning approach to 4296 Omicron viral genomes collected and deposited to GISAID as of December 14, 2021, and have identified a core haplotype of 28 polymutants (A67V, T95I, G339D, R346K, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H,
A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations.
Method: We therefore generated and used an Omicron Spike bearing the Q493R mutation for the full manuscript (Figures 1 and 2 and Figure S1).
Discussion: As i
Discussion: Of note, the sequence initially released for the Omicron Spike contained the Q493K substitution, but was then corrected to Q493R.
Discussion: Previous in vitro studies already showed the association of some of these mutations with increased infectivity, ACE2 interaction (N501Y, P681H), or immune evasion (K417N, N440K, G446S, S477N, E484A/K, Q493R).
Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients.
Abstract: We report that the Omicron brings an enhanced RBD-ACE2 interface through N501Y, Q493K/R, and T478K mutations; the changes further lead to unique interaction patterns, reminiscing the features of previously dominated variants, Alpha (N501Y) and Delta (L452R and T478K).
Introduction: Our study reveals that the Omicron mutations lead to an enhancement of binding between RBD and ACE2 by forming unique interaction patterns, which are caused mainly by N501Y, Q493K/R, and T478K mutations.
Method: To improve statistical results, 20 independent simulation runs of two Omicron variants
SARS_CoV_2 mutation literature information.
PMID: 
2022
International journal of molecular sciences
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