SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation C145A


Basic Characteristics of Mutations
Mutation Site C145A
Mutation Site Sentence The variant containing Mpro (C145A) behaved similarly to the WT reporter treated with a high concentration of GC376, only the unprocessed fusion protein was detectable.
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 Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39675720
Title The zymogenic form of SARS-CoV-2 main protease: A discrete target for drug discovery
Author Novotny P,Humpolickova J,Novakova V,Stanchev S,Strisovsky K,Zgarbova M,Weber J,Krystufek R,Starkova J,Hradilek M,Moravcova A,Gunterova J,Bach K,Majer P,Konvalinka J,Majerova T
Journal The Journal of biological chemistry
Journal Info 2025 Jan;301(1):108079
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M(pro)) autocatalytically releases itself out of the viral polyprotein to form a fully active mature dimer in a manner that is not fully understood. Here, we introduce several tools to help elucidate differences between cis (intramolecular) and trans (intermolecular) proteolytic processing and to evaluate inhibition of precursor M(pro). We found that many mutations at the P1 position of the N-terminal autoprocessing site do not block cis autoprocessing but do inhibit trans processing. Notably, substituting the WT glutamine at the P1 position with isoleucine retains M(pro) in an unprocessed precursor form that can be purified and further studied. We also developed a cell-based reporter assay suitable for compound library screening and evaluation in HEK293T cells. This assay can detect both overall M(pro) inhibition and the fraction of uncleaved precursor form of M(pro) through separable fluorescent signals. We observed that inhibitory compounds preferentially block mature M(pro). Bofutrelvir and a novel compound designed in-house showed the lowest selectivity between precursor and mature M(pro), indicating that inhibition of both forms may be possible. Additionally, we observed positive modulation of precursor activity at low concentrations of inhibitors. Our findings help expand understanding of the SARS-CoV-2 viral life cycle and may facilitate development of strategies to target precursor form of M(pro) for inhibition or premature activation of M(pro).
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.