SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation L452R


Basic Characteristics of Mutations
Mutation Site L452R
Mutation Site Sentence In contrast, these authors found that two substitutions uncommon in the global population, H505R (MAF = 0.001%) and Y515C (MAF = 0.004%), enhanced the entry of Alpha and Delta (L452R-T478K) variants and the Delta variants respectively, compared to the wild type ACE2.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RBD
Standardized Encoding Gene S  
Genotype/Subtype Kappa(B.1.617.1);Delta(B.1.617.2);Epsilon(B.1.427)
Viral Reference -
Functional Impact and Mechanisms
Disease COVID-19    
Immune -
Target Gene ACE2   
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 37520374
Title ACE2 receptor polymorphism in humans and animals increases the risk of the emergence of SARS-CoV-2 variants during repeated intra- and inter-species host-switching of the virus
Author Devaux CA,Fantini J
Journal Frontiers in microbiology
Journal Info 2023 Jul 13;14:1199561
Abstract Like other coronaviruses, SARS-CoV-2 has ability to spread through human-to-human transmission and to circulate from humans to animals and from animals to humans. A high frequency of SARS-CoV-2 mutations has been observed in the viruses isolated from both humans and animals, suggesting a genetic fitness under positive selection in both ecological niches. The most documented positive selection force driving SARS-CoV-2 mutations is the host-specific immune response. However, after electrostatic interactions with lipid rafts, the first contact between the virus and host proteins is the viral spike-cellular receptor binding. Therefore, it is likely that the first level of selection pressure impacting viral fitness relates to the virus's affinity for its receptor, the angiotensin I converting enzyme 2 (ACE2). Although sufficiently conserved in a huge number of species to support binding of the viral spike with enough affinity to initiate fusion, ACE2 is highly polymorphic both among species and within a species. Here, we provide evidence suggesting that when the viral spike-ACE2 receptor interaction is not optimal, due to host-switching, mutations can be selected to improve the affinity of the spike for the ACE2 expressed by the new host. Notably, SARS-CoV-2 is mutation-prone in the spike receptor binding domain (RBD), allowing a better fit for ACE2 orthologs in animals. It is possibly that this may also be true for rare human alleles of ACE2 when the virus is spreading to billions of people. In this study, we present evidence that human subjects expressing the rare E(329)G allele of ACE2 with higher allele frequencies in European populations exhibit a improved affinity for the SARS-CoV-2 spike N(501)Y variant of the virus. This may suggest that this viral N(501)Y variant emerged in the human population after SARS-CoV-2 had infected a human carrying the rare E(329)G allele of ACE2. In addition, this viral evolution could impact viral replication as well as the ability of the adaptive humoral response to control infection with RBD-specific neutralizing antibodies. In a shifting landscape, this ACE2-driven genetic drift of SARS-CoV-2 which we have named the 'boomerang effect', could complicate the challenge of preventing COVID with a SARS-CoV-2 spike-derived vaccine.
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.