HBV Mutation Detail Information

Virus Mutation HBV Mutation S202G


Basic Characteristics of Mutations
Mutation Site S202G
Mutation Site Sentence Southern blot analysis using wild-type HBV (HBVWT)-encoding-plasmid-transfected HepG2 cells revealed that CdFA efficiently suppresses the production of HBVWT (IC50 = 153.7 nM), entecavir (ETV)-resistant HBV carrying L180M/S202G/M204V substitutions (HBVETV(R); IC50 = 373.2 nM), and adefovir dipivoxil (ADV)-resistant HBV carrying A181T/N236T substitutions (HBVADV(R); IC50=192.6 nM), whereas ETV and ADV were less potent against HBVETV(R) and HBVADV(R) (IC50: >1,000 and 4,022.5 nM, respectively).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene P  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Entecavir(ETV)
Location -
Literature Information
PMID 32084506
Title 7-Deaza-7-fluoro modification confers on 4'-cyano-nucleosides potent activity against entecavir/adefovir-resistant HBV variants and favorable safety
Author Hayashi S,Higashi-Kuwata N,Das D,Tomaya K,Yamada K,Murakami S,Venzon DJ,Hattori SI,Isogawa M,Sarafianos SG,Mitsuya H,Tanaka Y
Journal Antiviral research
Journal Info 2020 Apr;176:104744
Abstract We designed, synthesized and identified a novel nucleoside derivative, 4'-C-cyano-7-deaza-7-fluoro-2'-deoxyadenosine (CdFA), which exerts potent anti-HBV activity (IC(50) ~26 nM) with favorable hepatocytotoxicity (CC(50) ~56 muM). Southern blot analysis using wild-type HBV (HBV(WT))-encoding-plasmid-transfected HepG2 cells revealed that CdFA efficiently suppresses the production of HBV(WT) (IC(50) = 153.7 nM), entecavir (ETV)-resistant HBV carrying L180M/S202G/M204V substitutions (HBV(ETV)(R); IC(50) = 373.2 nM), and adefovir dipivoxil (ADV)-resistant HBV carrying A181T/N236T substitutions (HBV(ADV)(R); IC(50=)192.6 nM), whereas ETV and ADV were less potent against HBV(ETV)(R) and HBV(ADV)(R) (IC(50): >1,000 and 4,022.5 nM, respectively). Once-daily peroral administration of CdFA to human-liver-chimeric mice over 14 days (1 mg/kg/day) comparably blocked HBV(WT) and HBV(ETV)(R) viremia by 0.7 and 1.2 logs, respectively, without significant changes in body-weight or serum human-albumin levels, although ETV only slightly suppressed HBV(ETV)(R) viremia (CdFA vs ETV; p = 0.032). Molecular modeling suggested that ETV-TP has good nonpolar interactions with HBV(WT) reverse transcriptase (RT(WT))'s Met204 and Asp205, while CdFA-TP fails to interact with Met204, in line with the relatively inferior activity against HBV(WT) of CdFA compared to ETV (IC(50): 0.026 versus 0.003 nM). In contrast, the 4'-cyano of CdFA-TP forms good nonpolar contacts with RT(WT)'s Leu180 and RT(ETV)(R)'s Met180, while ETV-TP loses interactions with RT(ETV)(R)'s Met180, explaining in part why ETV is less potent against HBV(ETV)(R) than CdFA. The present results show that CdFA exerts potent activity against HBV(WT), HBV(ETV)(R) and HBV(ADV)(R) with enhanced safety and that 7-deaza-7-fluoro modification confers potent activity against drug-resistant HBV variants and favorable safety, shedding light to further design more potent and safer anti-HBV nucleoside analogs.
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.