YFV Mutation Detail Information

Virus Mutation YFV Mutation S603T


Basic Characteristics of Mutations
Mutation Site S603T
Mutation Site Sentence We discovered that the analogous substitution in YFV (S603T) improved discrimination against the 2'-alpha-fluoro,2'-beta-modified uridine analogs.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NS5
Standardized Encoding Gene NS5
Genotype/Subtype -
Viral Reference NP_041726.1
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 40323779
Title Mechanism of Inhibition of the Active Triphosphate Form of 2'-alpha-Fluoro,2'-beta-bromouridine against Yellow Fever Virus RNA-Dependent RNA Polymerase
Author Gordon CJ,Walker SM,LeCher JC,Amblard F,Schinazi RF,Gotte M
Journal ACS infectious diseases
Journal Info 2025 Jun 13;11(6):1528-1538
Abstract Yellow fever virus (YFV) is a deadly mosquito-borne flavivirus that infects approximately 200,000 individuals each year. YFV outbreak and infection are persistent throughout South America and Africa, demonstrating significant epidemic potential. Although an approved and effective vaccine exists, the zoonotic nature of YFV undermines any potential eradication efforts, highlighting the need for effective, direct-acting antivirals. Essential for viral replication, RNA-dependent RNA polymerase (RdRp) is a proven therapeutic target. A prominent example includes sofosbuvir, a 2'-alpha-fluoro,2'-beta-methyluridine prodrug approved for the treatment of hepatitis C virus (HCV), that has demonstrated efficacy against YFV in vitro. A structurally similar 2'-alpha-fluoro, 2'-beta-bromouridine prodrug has exhibited potent anti-YFV activity both in vitro and in vivo. Here, we expressed the full-length nonstructural protein 5 from YFV in insect cells to investigate the active triphosphate form of these prodrugs. Enzyme kinetics indicate that both nucleotide analogs are incorporated less efficiently than UTP. Once incorporated, the analogs inhibit RNA synthesis through immediate chain termination. Omitting the 2'-beta-modification alleviates the inhibition of RNA synthesis, highlighting its role in eliciting an antiviral effect. S282T is a well-characterized mutation in motif B of HCV RdRp that confers resistance to sofosbuvir. We discovered that the analogous substitution in YFV (S603T) improved discrimination against the 2'-alpha-fluoro,2'-beta-modified uridine analogs. Collectively, our findings explain their observed anti-YFV activity and identify a conserved mechanism of resistance. Based on its in vivo efficacy and mechanism of action, the 2'-fluoro,2'-bromouridine prodrug shows potential for future therapeutic strategies against YFV.
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.