|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A363Y |
|
Mutation Site Sentence
|
We previously identified stabilizing space-filling mutations (Starr et al. 2020) that compensate for a loss of lipid tail volume that occupies space in the RBD core in the locked spike trimer structure (Toelzer et al. 2020), our deep mutational scanning map in BA.2.86 shows similar patterns of space-filling stabilizing mutations in the RBD core (e.g. I358F and A363Y), suggesting that the positive impact that these mutations had on RBD vaccine stability in earlier variants (Ellis et al. 2021) will continue in vaccine designs derived from BA.2.86. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
RBD |
|
Standardized Encoding Gene
|
S
|
|
Genotype/Subtype
|
BA.2.86 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
COVID-19
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
39310091
|
|
Title
|
Deep mutational scanning of SARS-CoV-2 Omicron BA.2.86 and epistatic emergence of the KP.3 variant
|
|
Author
|
Taylor AL,Starr TN
|
|
Journal
|
Virus evolution
|
|
Journal Info
|
2024 Sep 2;10(1):veae067
|
|
Abstract
|
Deep mutational scanning experiments aid in the surveillance and forecasting of viral evolution by providing prospective measurements of mutational effects on viral traits, but epistatic shifts in the impacts of mutations can hinder viral forecasting when measurements were made in outdated strain backgrounds. Here, we report measurements of the impact of all single amino acid mutations on ACE2-binding affinity and protein folding and expression in the SARS-CoV-2 Omicron BA.2.86 spike receptor-binding domain. As with other SARS-CoV-2 variants, we find a plastic and evolvable basis for receptor binding, with many mutations at the ACE2 interface maintaining or even improving ACE2-binding affinity. Despite its large genetic divergence, mutational effects in BA.2.86 have not diverged greatly from those measured in its Omicron BA.2 ancestor. However, we do identify strong positive epistasis among subsequent mutations that have accrued in BA.2.86 descendants. Specifically, the Q493E mutation that decreased ACE2-binding affinity in all previous SARS-CoV-2 backgrounds is reversed in sign to enhance human ACE2-binding affinity when coupled with L455S and F456L in the currently emerging KP.3 variant. Our results point to a modest degree of epistatic drift in mutational effects during recent SARS-CoV-2 evolution but highlight how these small epistatic shifts can have important consequences for the emergence of new SARS-CoV-2 variants.
|
|
Sequence Data
|
PRJNA770094
|