SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation D48N


Basic Characteristics of Mutations
Mutation Site D48N
Mutation Site Sentence Structural Basis for the Inhibition of SARS-CoV-2 Mpro D48N Mutant by Shikonin and PF-07321332.
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 -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 38257765
Title Structural Basis for the Inhibition of SARS-CoV-2 M(pro) D48N Mutant by Shikonin and PF-07321332
Author Zhao Z,Zhu Q,Zhou X,Li W,Yin X,Li J
Journal Viruses
Journal Info 2023 Dec 30;16(1):65
Abstract Preventing the spread of SARS-CoV-2 and its variants is crucial in the fight against COVID-19. Inhibition of the main protease (M(pro)) of SARS-CoV-2 is the key to disrupting viral replication, making M(pro) a promising target for therapy. PF-07321332 and shikonin have been identified as effective broad-spectrum inhibitors of SARS-CoV-2 M(pro). The crystal structures of SARS-CoV-2 M(pro) bound to PF-07321332 and shikonin have been resolved in previous studies. However, the exact mechanism regarding how SARS-CoV-2 M(pro) mutants impact their binding modes largely remains to be investigated. In this study, we expressed a SARS-CoV-2 M(pro) mutant, carrying the D48N substitution, representing a class of mutations located near the active sites of M(pro). The crystal structures of M(pro) D48N in complex with PF-07321332 and shikonin were solved. A detailed analysis of the interactions between M(pro) D48N and two inhibitors provides key insights into the binding pattern and its structural determinants. Further, the binding patterns of the two inhibitors to M(pro) D48N mutant and wild-type M(pro) were compared in detail. This study illustrates the possible conformational changes when the M(pro) D48N mutant is bound to inhibitors. Structural insights derived from this study will inform the development of new drugs against novel coronaviruses.
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.