SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation N501Y


Basic Characteristics of Mutations
Mutation Site N501Y
Mutation Site Sentence Moreover, we revealed that the mutation N501Y in the viral spike protein has a crucial role in determining the infectivity of cells expressing murine ACE2 and of mice in vivo.
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 Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 40353671
Title Determinants of susceptibility to SARS-CoV-2 infection in murine ACE2
Author Kondo T,Suzuki R,Yajima H,Kawahara S,Yamaya K,Ichikawa T,Tsujino S,Suzuki S,Tamura T,Hashiguchi T,Fukuhara T
Journal Journal of virology
Journal Info 2025 Jun 17;99(6):e0054325
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor to enter host cells, and primary receptor recognition of the spike protein is a major determinant of the host range of SARS-CoV-2. Since the emergence of SARS-CoV-2, a considerable number of variants have emerged. However, the determinants of host tropism of SARS-CoV-2 remain elusive. We conducted infection assays with chimeric recombinant SARS-CoV-2 carrying the spike protein from 10 viral variants, assessing their entry efficiency using mammalian ACE2 orthologs from species that have close contact with humans. We found that only murine ACE2 exhibited different susceptibilities to infection with the SARS-CoV-2 variants. Moreover, we revealed that the mutation N501Y in the viral spike protein has a crucial role in determining the infectivity of cells expressing murine ACE2 and of mice in vivo. Next, we identified six amino acid substitutions at 24, 30, 31, 82, 83, and 353 in murine ACE2 that allowed for viral entry of the variants to which murine ACE2 was previously resistant. Furthermore, we showed that ACE2 from a species closely related to mice, Mus caroli, is capable of supporting entry of the viral variants that could not use murine ACE2. These results suggest that few ACE2 orthologs have different susceptibility to infection with SARS-CoV-2 variants as observed for murine ACE2. Collectively, our study reveals critical amino acids in ACE2 and the SARS-CoV-2 spike protein that are involved in the host tropism of SARS-CoV-2, shedding light on interspecies susceptibility to infection.IMPORTANCESARS-CoV-2 can infect many species besides humans, leading to the evolution of the virus and adaptation to other animal hosts, which could trigger a new COVID-19 wave. The SARS-CoV-2 spike protein utilizes ACE2 as a receptor for entry into host cells. The interaction of ACE2 with the spike protein determines the host range of SARS-CoV-2. In this study, using chimeric viruses carrying the spike protein of SARS-CoV-2 variants to infect cells expressing different ACE2 orthologs from species humans come in close contact with, we confirmed murine ACE2 alone showed different susceptibility to the variants. We identified residues in murine ACE2 and the viral spike that restrict viral entry. Furthermore, an ACE2 ortholog from a species genetically close to mice mediated entry of SARS-CoV-2 variants incapable of infecting mice. This research highlights the uniquely limited susceptibility of mice to different SARS-CoV-2 variants and provides invaluable insights into the host tropism 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.