SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation Y54A


Basic Characteristics of Mutations
Mutation Site Y54A
Mutation Site Sentence Additionally, simnotrelvir demonstrated effective inhibition against several nirmatrelvir-resistant SARS-CoV-2 3CLpro mutants, including A260V, Y54A, (T21I + S144A), F140A, H172Y, and E166V.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region 3CLpro
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
Location -
Literature Information
PMID 40062859
Title Potent antiviral activity of simnotrelvir against key epidemic SARS-CoV-2 variants with a high resistance barrier
Author Zhao L,Li C,Wang M,Zhou M,Jiang L,Zhang W,Yu J,Wang W,Zhou K,Pan K,Lam H-Y,Hung IF-N,Chan K-H,Liu L,Wang F,Zhao X,Chen Y
Journal Antimicrobial agents and chemotherapy
Journal Info 2025 Apr 2;69(4):e0155624
Abstract Simnotrelvir is an oral small-molecule antiviral agent targeting the 3C-like protease (3CL(pro)) of SARS-CoV-2, proven effective against the Delta variant with favorable pharmacokinetics and safety in preclinical study. In this study, we further evaluated the antiviral efficacy of simnotrelvir against a range of emerging Omicron variants, including BA.1, BA.4, BA.5, CH.1.1, XBB.1.5, XBB.1.16, EG.5, and JN.1. In vitro assays with Vero E6 cells confirmed that simnotrelvir exhibited robust antiviral activity across these variants, comparable to the Food and Drug Administration (FDA)-approved drug nirmatrelvir. Additionally, simnotrelvir demonstrated effective inhibition against several nirmatrelvir-resistant SARS-CoV-2 3CL(pro) mutants, including A260V, Y54A, (T21I + S144A), F140A, H172Y, and E166V. Importantly, simnotrelvir showed better potency against the E166V mutation compared to nirmatrelvir. Resistance selection studies revealed that BA.5 developed reduced sensitivity after 5 and 10 passages, increasing the IC(50) values by 3.2 and 4.5-fold, respectively, while HCoV-OC43 showed an 8.3-fold increase after 12 passages. Despite this, simnotrelvir's overall efficacy remains strong. Furthermore, clinical trials demonstrated that combining simnotrelvir with ritonavir significantly shortened symptom resolution in COVID-19 patients. Genomic analysis of treated patients found random nucleotide substitutions but no significant mutations linked to 3CL(pro) resistance. In conclusion, simnotrelvir shows strong antiviral activity against SARS-CoV-2 variants and maintains a high barrier to resistance, reinforcing its potential as an effective therapeutic option for current and future SARS-CoV-2 variants.
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.