SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation P132H


Basic Characteristics of Mutations
Mutation Site P132H
Mutation Site Sentence These VOC/VOI carry prevalent mutations at varying frequencies in the Mpro specifically for: alpha, beta, gamma (K90R), lambda (G15S) and omicron (P132H).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region Mpro
Standardized Encoding Gene ORF1a  
Genotype/Subtype Omicron
Viral Reference -
Functional Impact and Mechanisms
Disease COVID-19    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 35461811
Title Structural basis for the in vitro efficacy of nirmatrelvir against SARS-CoV-2 variants
Author Greasley SE,Noell S,Plotnikova O,Ferre R,Liu W,Bolanos B,Fennell K,Nicki J,Craig T,Zhu Y,Stewart AE,Steppan CM
Journal The Journal of biological chemistry
Journal Info 2022 Jun;298(6):101972
Abstract The COVID-19 pandemic continues to be a public health threat with emerging variants of SARS-CoV-2. Nirmatrelvir (PF-07321332) is a reversible, covalent inhibitor targeting the main protease (M(pro)) of SARS-CoV-2 and the active protease inhibitor in PAXLOVID (nirmatrelvir tablets and ritonavir tablets). However, the efficacy of nirmatrelvir is underdetermined against evolving SARS-CoV-2 variants. Here, we evaluated the in vitro catalytic activity and potency of nirmatrelvir against the M(pro) of prevalent variants of concern (VOCs) or variants of interest (VOIs): Alpha (alpha, B.1.1.7), Beta (beta, B.1.351), Delta (delta, B1.617.2), Gamma (gamma, P.1), Lambda (lambda, B.1.1.1.37/C37), Omicron (omicron, B.1.1.529), as well as the original Washington or wildtype strain. These VOCs/VOIs carry prevalent mutations at varying frequencies in the M(pro) specifically for alpha, beta, gamma (K90R), lambda (G15S), and omicron (P132H). In vitro biochemical enzymatic assay characterization of the enzyme kinetics of the mutant M(pros) demonstrates that they are catalytically comparable to wildtype. We found that nirmatrelvir has similar potency against each mutant M(pro) including P132H that is observed in the Omicron variant with a Ki of 0.635 nM as compared to a Ki of 0.933 nM for wildtype. The molecular basis for these observations were provided by solution-phase structural dynamics and structural determination of nirmatrelvir bound to the omicron, lambda, and beta M(pro) at 1.63 to 2.09 A resolution. These in vitro data suggest that PAXLOVID has the potential to maintain plasma concentrations of nirmatrelvir many-fold times higher than the amount required to stop the SARS-CoV-2 VOC/VOI, including Omicron, from replicating in cells.
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.