SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation D48E


Basic Characteristics of Mutations
Mutation Site D48E
Mutation Site Sentence However,we report the following new findings from the variants: (1) Residues GLY15,VAL157,and PRO184 have mutated more than once in SARS CoV-2, (2) the D48E variant has lead to a novel ""TSEEMLN"""" loop at the binding pocket, (3) inactive apo Mpro does not show signs of dissociation in 100 ns MD, (4) a non-canonical pose for PHE140 widens the substrate binding surface, (5) dual allosteric pockets coinciding with various stabilizing and functional components of the substrate binding pocket were found to display correlated compaction dynamics, (6) high betweenness centrality values for residues 17 and 128 in all Mpro samples suggest their high importance in dimer stability-one such consequence has been observed for the M17I mutation whereby one of the N-fingers was highly unstable.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region Mpro
Standardized Encoding Gene ORF1a  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 32853525
Title Impact of Early Pandemic Stage Mutations on Molecular Dynamics of SARS-CoV-2 M(pro)
Author Sheik Amamuddy O,Verkhivker GM,Tastan Bishop O
Journal Journal of chemical information and modeling
Journal Info 2020 Oct 26;60(10):5080-5102
Abstract A new coronavirus (SARS-CoV-2) is a global threat to world health and economy. Its dimeric main protease (M(pro)), which is required for the proteolytic cleavage of viral precursor proteins, is a good candidate for drug development owing to its conservation and the absence of a human homolog. Improving our understanding of M(pro) behavior can accelerate the discovery of effective therapies to reduce mortality. All-atom molecular dynamics (MD) simulations (100 ns) of 50 mutant M(pro) dimers obtained from filtered sequences from the GISAID database were analyzed using root-mean-square deviation, root-mean-square fluctuation, R(g), averaged betweenness centrality, and geometry calculations. The results showed that SARS-CoV-2 M(pro) essentially behaves in a similar manner to its SAR-CoV homolog. However, we report the following new findings from the variants: (1) Residues GLY15, VAL157, and PRO184 have mutated more than once in SARS CoV-2; (2) the D48E variant has lead to a novel ""TSEEMLN"""" loop at the binding pocket; (3) inactive apo M(pro) does not show signs of dissociation in 100 ns MD; (4) a non-canonical pose for PHE140 widens the substrate binding surface; (5) dual allosteric pockets coinciding with various stabilizing and functional components of the substrate binding pocket were found to display correlated compaction dynamics; (6) high betweenness centrality values for residues 17 and 128 in all M(pro) samples suggest their high importance in dimer stability-one such consequence has been observed for the M17I mutation whereby one of the N-fingers was highly unstable. (7) Independent coarse-grained Monte Carlo simulations suggest a relationship between the rigidity/mutability and enzymatic function. Our entire approach combining database preparation, variant retrieval, homology modeling, dynamic residue network (DRN), relevant conformation retrieval from 1-D kernel density estimates from reaction coordinates to other existing approaches of structural analysis, and data visualization within the coronaviral M(pro) is also novel and is applicable to other coronaviral proteins.
Sequence Data EPI_ISL_425242
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.