SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation D222Y


Basic Characteristics of Mutations
Mutation Site D222Y
Mutation Site Sentence We also identified disadvantageous substitutions, NSP13-M233I and NSP14-D222Y, that reduced BQ.1.1 and XBB.1.16 replication, respectively.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NSP14
Standardized Encoding Gene ORF1b  
Genotype/Subtype BQ.1.1;XBB.1.16
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 40358207
Title The NSP6-L260F substitution in SARS-CoV-2 BQ.1.1 and XBB.1.16 lineages compensates for the reduced viral polymerase activity caused by mutations in NSP13 and NSP14
Author Furusawa Y,Iwatsuki-Horimoto K,Yamayoshi S,Kawaoka Y
Journal Journal of virology
Journal Info 2025 Jun 17;99(6):e0065625
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants emerged at the end of 2021, and their subvariants are still circulating worldwide. While changes in the S protein of these variants have been extensively studied, the roles of amino acid substitutions in non-structural proteins have not been fully revealed. In this study, we found that SARS-CoV-2 bearing the NSP6-L260F substitution emerged repeatedly when we generated several SARS-CoV-2 variants by reverse genetics or when we passaged SARS-CoV-2 isolated from clinical samples and that it was selected under cell culture conditions. Although this substitution has been detected in BQ.1.1 and XBB.1.16 that circulated in nature, its effect on viral properties is unclear. Here, we generated SARS-CoV-2 with or without the NSP6-L260F by reverse genetics and found that NSP6-L260F promotes virus replication in vitro and in vivo by increasing viral polymerase activity and enhancing virus pathogenicity in hamsters. We also identified disadvantageous substitutions, NSP13-M233I and NSP14-D222Y, that reduced BQ.1.1 and XBB.1.16 replication, respectively. These adverse effects were compensated for by NSP6-L260F. Our findings suggest the importance of NSP6-L260F for virus replication and pathogenicity and reveal part of the evolutionary process of Omicron variants.IMPORTANCEAlthough the properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants continue to change through the acquisition of various amino acid substitutions, the roles of the amino acid substitutions in the non-structural proteins have not been fully explored. In this study, we found that the NSP6-L260F substitution enhances viral polymerase activity and is important for viral replication and pathogenicity. In addition, we found that the NSP13-M233I substitution in the BQ.1.1 lineage and the NSP14-D222Y substitution in the XBB.1.16 lineage reduce viral polymerase activity, and this adverse effect is compensated for by the NSP6-L260F substitution. Our results provide insight into the evolutionary process of SARS-CoV-2.
Sequence Data -
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.