SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation D164G


Basic Characteristics of Mutations
Mutation Site D164G
Mutation Site Sentence A stabilized version of the trimeric S protein (VFLIP) harboring the D164G mutation was mixed with 4C12-B12 Fab at a spike:Fab molar ratio of 1:3 and incubated for 30 min at RT before grids were frozen.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region S
Standardized Encoding Gene S  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease COVID-19    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location Sydney(Australia)
Literature Information
PMID 39746041
Title Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies
Author Mazigi O,Langley DB,Henry JY,Burnett DL,Sobti M,Walker GJ,Rouet R,Balachandran H,Lenthall H,Jackson J,Ubiparipovic S,Schofield P,Brown SHJ,Schulz SR,Hoffmann M,Pohlmann S,Post J,Martinello M,Ahlenstiel G,Kelleher A,Rawlinson WD,Turville SG,Bull RA,Stewart AG,Jack HM,Goodnow CC,Christ D
Journal Proceedings of the National Academy of Sciences of the United States of America
Journal Info 2025 Jan 7;122(1):e2417544121
Abstract The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the ""up"" conformation of the SARS-CoV-2 spike trimer. Increasing antibody affinity into the low picomolar range endowed potent neutralization of VOCs and protection of hACE2 mice from viral challenge. Cryoelectron microscopy and crystal structures of two affinity-matured antibodies (4C12-B12 and 4G1-C2) in complex with RBD highlighted binding modes and epitopes distal from mutational hotspots commonly overserved in VOCs, providing direct structural insights into the observed mutational resistance. Moreover, we further demonstrate that antibodies targeting the class 6 epitope, rather than being an artifact of in vitro selection, are common in the IgG1(+) memory B cell repertoire of convalescent patients and can be induced in human antibody V-gene transgenic mice through immunization. Our results highlight the importance of very high (picomolar) affinity in the development of neutralizing antibodies and vaccines and suggest an affinity threshold in the provision of broad and long-lasting immunity against 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.