SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation Q493E


Basic Characteristics of Mutations
Mutation Site Q493E
Mutation Site Sentence Additionally, our analysis showed that the L455S and Q493E mutations in the RBD can influence spike cleavage, offering new insights into SARS-CoV-2 spike biology.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RBD
Standardized Encoding Gene S  
Genotype/Subtype KP.3
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 40298448
Title Comparative analysis of replication and immune evasion among SARS-CoV-2 subvariants BA.2.86, JN.1, KP.2, and KP.3
Author Hu Y,Zou J,Nguyen MD,Chang HC,Yeung J,Hao H,Shi P-Y,Ren P,Xie X
Journal mBio
Journal Info 2025 Jun 11;16(6):e0350324
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2.86 sublineage and its descendants (JN.1, KP.2, and KP.3) have acquired key recurrent mutations (R346T, L455S, F456L, and Q493E) and became predominant strains, following the epidemiological progression: BA.2.86-->JN.1-->KP.2-->KP.3. However, the mechanisms driving this succession remain incompletely understood. In this study, we assessed the replication fitness of SARS-CoV-2 strains containing spike sequences from BA.2.86 and its descendants (JN.1, KP.2, and KP.3) in primary human airway epithelium cells and their sensitivity to neutralization by human sera. Our analysis revealed reduced spike cleavage in JN.1 and KP.2 virions compared to BA.2.86 and KP.3, indicating that receptor-binding domain (RBD) mutations L455S and Q493E, despite being distant from the furin cleavage site, can influence spike cleavage. JN.1, with the additional L455S mutation, replicated more slowly than BA.2.86 but was more resistant to neutralization by XBB.1.5-infection sera, suggesting that immune evasion driven by the L455S mutation is the primary factor behind the BA.2.86-to-JN.1 transition. KP.2, carrying additional R346T, L455S, and F456L mutations, showed both enhanced replication and increased resistance to neutralization by JN.1-infection sera, indicating that the combined effects of these mutations on immune evasion and viral fitness drive the JN.1-to-KP.2 shift. The latest strain, KP.3, derived from JN.1 with the L455S, F456L, and Q493E mutations, demonstrated even greater replication than KP.2 while maintaining similar neutralization sensitivity to JN.1-infection sera, suggesting that Q493E further enhances viral replication and drives the KP.2-to-KP.3 transition. These findings highlight how specific recurrent spike mutations in BA.2.86 descendants fine-tune viral replication fitness and immune evasion, promoting their emergence and dominance. IMPORTANCE: The study advances our understanding of the roles of immune evasion and replication fitness in driving the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the BA.2.86 sublineage to its descendants (JN.1, KP.2, and KP.3). Through head-to-head comparisons of the replication fitness of recombinant SARS-CoV-2 strains containing spike sequences from BA.2.86 and its descendants in primary human airway epithelium cells, alongside assessments of their neutralization sensitivity to human sera, we revealed how recurrent mutations R346T, L455S, F456L, and Q493E in the receptor-binding domain (RBD) fine-tune immune evasion and viral replication fitness, underscoring the critical need for updated countermeasures to combat newly emerged SARS-CoV-2 variants. Additionally, our analysis showed that the L455S and Q493E mutations in the RBD can influence spike cleavage, offering new insights into SARS-CoV-2 spike biology.
Sequence Data EPI_ISL_18110065;EPI_ISL_18237538;EPI_ISL_ 19002640;EPI_ISL_19016982
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.