SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation L50A


Basic Characteristics of Mutations
Mutation Site L50A
Mutation Site Sentence For comparison, the L50A mutant was also constructed to investigate the contribution of the original leucine side chain to the enzyme activity.
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 39893201
Title Distal protein-protein interactions contribute to nirmatrelvir resistance
Author Lewandowski EM,Zhang X,Tan H,Jaskolka-Brown A,Kohaal N,Frazier A,Madsen JJ,Jacobs LMC,Wang J,Chen Y
Journal Nature communications
Journal Info 2025 Feb 1;16(1):1266
Abstract SARS-CoV-2 main protease, M(pro), is responsible for processing the viral polyproteins into individual proteins, including the protease itself. M(pro) is a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g., E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g., P252L, T21I, L50F), which restore the fitness of viral replication. To probe the role of the non-active site mutations in fitness rescue, here we use an M(pro) triple mutant (L50F/E166A/L167F) that confers nirmatrelvir drug resistance with a viral fitness level similar to the wild-type. By comparing peptide and full-length M(pro) protein as substrates, we demonstrate that the binding of M(pro) substrate involves more than residues in the active site. Particularly, L50F and other non-active site mutations can enhance the M(pro) dimer-dimer interactions and help place the nsp5-6 substrate at the enzyme catalytic center. The structural and enzymatic activity data of M(pro) L50F, L50F/E166A/L167F, and others underscore the importance of considering the whole substrate protein in studying M(pro) and substrate interactions, and offers important insights into M(pro) function, resistance development, and inhibitor design.
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.