SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation L452W


Basic Characteristics of Mutations
Mutation Site L452W
Mutation Site Sentence However, several members of this group have been found to be susceptible to the substitution of L452 by an arginine (L452R), glutamine (L452Q), or tryptophan (L452W) residue, as found in the VOC Delta, VOI Lambda, and several of the later Omicron variants, such as BA.2.86, XBB.1.5, and DV.7.1 (29) and therefore have a reduced capacity to neutralize these SARS-CoV-2 variants.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region
Standardized Encoding Gene
Genotype/Subtype BA.2.86
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune Y
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39494911
Title A human monoclonal antibody neutralizing SARS-CoV-2 Omicron variants containing the L452R mutation
Author Stein SC,Hansen G,Ssebyatika G,Stroh LJ,Ochulor O,Herold E,Schwarzloh B,Mutschall D,Zischke J,Cordes AK,Schneider T,Hinrichs I,Blasczyk R,Kleine-Weber H,Hoffmann M,Klein F,Kaiser FK,Gonzalez-Hernandez M,Armando F,Ciurkiewicz M,Beythien G,Pohlmann S,Baumgartner W,Osterhaus A,Schulz TF,Krey T
Journal Journal of virology
Journal Info 2024 Dec 17;98(12):e0122324
Abstract The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by the emergence of variants of concern (VOCs), which have acquired mutations to escape neutralizing antibodies (nAbs). These mutations are not evenly distributed on the RBD surface but cluster on several distinct surfaces, suggesting an influence of the targeted epitope on the capacity to neutralize a broad range of VOCs. Here, we identified a potent nAb from convalescent patients targeting the receptor-binding domain of a broad range of SARS-CoV-2 VOCs. Except for the Lambda and BA.2.86 variants, this nAb efficiently inhibited the entry of most tested VOCs, including Omicron subvariants BA.1, BA.2, XBB.1.5, and EG.5.1 and to a limited extent also BA.4/5, BA.4.6, and BQ.1.1. It bound recombinant S protein with picomolar affinity, reduced the viral load in the lung of infected hamsters, and prevented the severe lung pathology typical for SARS-CoV-2 infections. An X-ray structure of the nAb-RBD complex revealed an epitope that does not fall into any of the conventional classes and provided insights into its broad neutralization properties. Our findings highlight a conserved epitope within the SARS-CoV-2 RBD that should be preferably targeted by therapeutic antibodies and inform rational vaccine development.IMPORTANCETherapeutic antibodies are effective in preventing severe disease from SARS-CoV-2 infection and constitute an important option in pandemic preparedness, but mutations within the S protein of virus variants (e.g., a mutation of L452) confer resistance to many of such antibodies. Here, we identify a human antibody targeting the S protein receptor-binding domain (RBD) with an elevated escape barrier and characterize its interaction with the RBD functionally and structurally at the atomic level. A direct comparison with reported antibodies targeting the same epitope illustrates important differences in the interface, providing insights into the breadth of antibody binding. These findings highlight the relevance of an extended neutralization profiling in combination with biochemical and structural characterization of the antibody-RBD interaction for the selection of future therapeutic antibodies, which may accelerate the control of potential future pandemics.
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.