SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation H655Y


Basic Characteristics of Mutations
Mutation Site H655Y
Mutation Site Sentence Long-range enhancement of N501Y-endowed mouse infectivity of SARS-CoV-2 by the non-RBD mutations of Ins215KLRS and H655Y.
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 -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 35658928
Title Long-range enhancement of N501Y-endowed mouse infectivity of SARS-CoV-2 by the non-RBD mutations of Ins215KLRS and H655Y
Author Zhu Y,Zhou W,Niu Z,Sun J,Zhang Z,Li Q,Zheng Y,Wang C,Gao L,Sun Q
Journal Biology direct
Journal Info 2022 Jun 5;17(1):14
Abstract BACKGROUND: Rodents, such as mice, are vulnerable targets, and potential intermediate hosts, of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, and Omicron. N501Y in the receptor-binding domain (RBD) of Spike protein is the key mutation dictating the mouse infectivity, on which the neighboring mutations within RBD have profound impacts. However, the impacts of mutations outside RBD on N501Y-mediated mouse infectivity remain to be explored. RESULTS: Herein, we report that two non-RBD mutations derived from mouse-adapted strain, Ins215KLRS in the N-terminal domain (NTD) and H655Y in the subdomain linking S1 to S2, enhance mouse infectivity in the presence of N501Y mutation, either alone or together. This is associated with increased interaction of Spike with mouse ACE2 and mutations-induced local conformation changes in Spike protein. Mechanistically, the H655Y mutation disrupts interaction with N657, resulting in a less tight loop that wraps the furin-cleavage finger; and the insertion of 215KLRS in NTD increases its intramolecular interaction with a peptide chain that interfaced with the RBD-proximal region of the neighboring protomer, leading to a more flexible RBD that facilitates receptor binding. Moreover, the Omicron Spike that contains Ins214EPE and H655Y mutations confer mouse infectivity > 50 times over the N501Y mutant, which could be effectively suppressed by mutating them back to wild type. CONCLUSIONS: Collectively, our study sheds light on the cooperation between distant Spike mutations in promoting virus infectivity, which may undermine the high infectiousness of Omicron variants towards mice.
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.