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Basic Characteristics of Mutations
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Mutation Site
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E484K |
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Mutation Site Sentence
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Furthermore, significant decreases in IgG recognition to various point mutations, including G446S (5.4-fold reduction, p < 0.0001) found in Omicron, E484K (5.9-fold reduction, p < 0.0001) found in Gamma and Beta, as well as F490S (5.4-fold reduction, p < 0.0001) and N501T (6.8-fold reduction, p < 0.0001) (Fig. 1C). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RBD |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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Gamma;Beta |
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Viral Reference
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"spike S1 (Sino Biological; 40,591-V08H), spike S2 (ACRO Biosystems; S2N-C52H5), nucleoprotein (ACRO Biosystems; NUN-C5227) and spike trimer (provided by Adam Wheatley)"
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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ACE2
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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Australia |
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Literature Information
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PMID
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37477828
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Title
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Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants
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Author
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Haycroft ER,Davis SK,Ramanathan P,Lopez E,Purcell RA,Tan LL,Pymm P,Wines BD,Hogarth PM,Wheatley AK,Juno JA,Redmond SJ,Gherardin NA,Godfrey DI,Tham WH,Selva KJ,Kent SJ,Chung AW
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Journal
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Medical microbiology and immunology
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Journal Info
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2023 Aug;212(4):291-305
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Abstract
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Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as FcgammaRIIa- and FcgammaRIIIa-binding antibodies, in plasma from two-dose BNT162b2-vaccine recipients and mild-COVID-19 convalescent subjects obtained during the first wave using a custom-designed bead-based 39-plex array. IgG-recognition and FcgammaR-binding antibodies were decreased against the RBD of Beta and Omicron, as well as point mutation G446S, found in several Omicron sub-variants as compared to wild type. Notably, while there was a profound decrease in ACE2 inhibition against Omicron, FcgammaR-binding antibodies were less affected, suggesting that Fc functional antibody responses may be better retained against the RBD of Omicron in comparison to neutralization. Furthermore, while measurement of RBD-ACE2-binding affinity via biolayer interferometry showed that all VOC RBDs have enhanced affinity to human ACE2, we demonstrate that human ACE2 polymorphisms, E35K (rs1348114695) has reduced affinity to VOCs, while K26R (rs4646116) and S19P (rs73635825) have increased binding kinetics to the RBD of VOCs, potentially affecting virus-host interaction and, thereby, host susceptibility. Collectively, our findings provide in-depth coverage of the impact of RBD mutations on key facets of host-virus interactions.
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Sequence Data
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-
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