SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation E166V


Basic Characteristics of Mutations
Mutation Site E166V
Mutation Site Sentence It is worthy that C5N17B retains antiviral activity against nirmatrelvir-resistant strains with T21I/E166V and L50F/E166V mutations in Mpro (EC50 = 0.26 and 0.15 microM, respectively).
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 nirmatrelvir;ensitrelvir
Location -
Literature Information
PMID 39319611
Title Miniaturized Modular Click Chemistry-enabled Rapid Discovery of Unique SARS-CoV-2 M(pro) Inhibitors With Robust Potency and Drug-like Profile
Author Yang M,Lee MK,Gao S,Song L,Jang HY,Jo I,Yang CC,Sylvester K,Ko C,Wang S,Ye B,Tang K,Li J,Gu M,Muller CE,Strater N,Liu X,Kim M,Zhan P
Journal Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Journal Info 2024 Nov;11(43):e2404884
Abstract The COVID-19 pandemic has required an expeditious advancement of innovative antiviral drugs. In this study, focused compound libraries are synthesized in 96- well plates utilizing modular click chemistry to rapidly discover potent inhibitors targeting the main protease (M(pro)) of SARS-CoV-2. Subsequent direct biological screening identifies novel 1,2,3-triazole derivatives as robust M(pro) inhibitors with high anti-SARS-CoV-2 activity. Notably, C5N17B demonstrates sub-micromolar M(pro) inhibitory potency (IC(50) = 0.12 microM) and excellent antiviral activity in Calu-3 cells determined in an immunofluorescence-based antiviral assay (EC(50) = 0.078 microM, no cytotoxicity: CC(50) > 100 microM). C5N17B shows superior potency to nirmatrelvir (EC(50) = 1.95 microM) and similar efficacy to ensitrelvir (EC(50) = 0.11 microM). Importantly, this compound displays high antiviral activities against several SARS-CoV-2 variants (Gamma, Delta, and Omicron, EC(50) = 0.13 - 0.26 microM) and HCoV-OC43, indicating its broad-spectrum antiviral activity. It is worthy that C5N17B retains antiviral activity against nirmatrelvir-resistant strains with T21I/E166V and L50F/E166V mutations in M(pro) (EC(50) = 0.26 and 0.15 microM, respectively). Furthermore, C5N17B displays favorable pharmacokinetic properties. Crystallography studies reveal a unique, non-covalent multi-site binding mode. In conclusion, these findings substantiate the potential of C5N17B as an up-and-coming drug candidate targeting SARS-CoV-2 M(pro) for clinical therapy.
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.