SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation C145A


Basic Characteristics of Mutations
Mutation Site C145A
Mutation Site Sentence Thus,it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of Mpro,the main cysteine protease of SARS-CoV-2,but not with catalytically active wild-type Mpro.
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 COVID-19    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 32984400
Title Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral M(pro) Protease Target Host Selenoproteins and Glutathione Synthesis?
Author Taylor EW,Radding W
Journal Frontiers in nutrition
Journal Info 2020 Sep 2;7:143
Abstract Glutathione peroxidases (GPX), a family of antioxidant selenoenzymes, functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Thus, it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of M(pro), the main cysteine protease of SARS-CoV-2, but not with catalytically active wild-type M(pro). This seemingly anomalous result is what might be expected if GPX1 is a substrate for the active protease, leading to its fragmentation. We show that the GPX1 active site sequence is substantially similar to a known M(pro) cleavage site, and is identified as a potential cysteine protease site by the Procleave algorithm. Proteolytic knockdown of GPX1 is highly consistent with previously documented effects of recombinant SARS-CoV M(pro) in transfected cells, including increased reactive oxygen species and NF-kappaB activation. Because NF-kappaB in turn activates many pro-inflammatory cytokines, this mechanism could contribute to increased inflammation and cytokine storms observed in COVID-19. Using web-based protease cleavage site prediction tools, we show that M(pro) may be targeting not only GPX1, but several other selenoproteins including SELENOF and thioredoxin reductase 1, as well as glutamate-cysteine ligase, the rate-limiting enzyme for glutathione synthesis. This hypothesized proteolytic knockdown of components of both the thioredoxin and glutaredoxin systems is consistent with a viral strategy to inhibit DNA synthesis, to increase the pool of ribonucleotides for RNA synthesis, thereby enhancing virion production. The resulting ""collateral damage"" of increased oxidative stress and inflammation would be exacerbated by dietary deficiencies of selenium and glutathione precursors.
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.