SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation H41H


Basic Characteristics of Mutations
Mutation Site H41H
Mutation Site Sentence Though neutron crystallography suggested an ion pair of C145-/H41H+ adopted in apo SARS-CoV-2 3CLpro, an experimental study on the pH-dependent kinetic parameters of SARS-CoV-2 3CLpro and various computational simulations proposed that the apo enzyme favors the neutral form of C145/H41.
Mutation Level Amino acid level
Mutation Type Synonymous substitution
Gene/Protein/Region 3CLpro
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 37181765
Title Unraveling the catalytic mechanism of SARS-CoV-2 papain-like protease with allosteric modulation of C270 mutation using multiscale computational approaches
Author Shao Q,Xiong M,Li J,Hu H,Su H,Xu Y
Journal Chemical science
Journal Info 2023 Apr 11;14(18):4681-4696
Abstract Papain-like protease (PL(pro)) is a promising therapeutic target against SARS-CoV-2, but its restricted S1/S2 subsites pose an obstacle in developing active site-directed inhibitors. We have recently identified C270 as a novel covalent allosteric site for SARS-CoV-2 PL(pro) inhibitors. Here we present a theoretical investigation of the proteolysis reaction catalyzed by the wild-type SARS-CoV-2 PL(pro) as well as the C270R mutant. Enhanced sampling MD simulations were first performed to explore the influence of C270R mutation on the protease dynamics, and sampled thermodynamically favorable conformations were then submitted to MM/PBSA and QM/MM MD simulations for thorough characterization of the protease-substrate binding and covalent reactions. The disclosed proteolysis mechanism of PL(pro), as characterized by the occurrence of proton transfer from the catalytic C111 to H272 prior to the substrate binding and with deacylation being the rate-determining step of the whole proteolysis process, is not completely identical to that of the 3C-like protease, another key cysteine protease of coronaviruses. The C270R mutation alters the structural dynamics of the BL2 loop that indirectly impairs the catalytic function of H272 and reduces the binding of the substrate with the protease, ultimately showing an inhibitory effect on PL(pro). Together, these results provide a comprehensive understanding at the atomic level of the key aspects of SARS-CoV-2 PL(pro) proteolysis, including the catalytic activity allosterically regulated by C270 modification, which is crucial to the follow-up inhibitor design and development.
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.