SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation N82W


Basic Characteristics of Mutations
Mutation Site N82W
Mutation Site Sentence Finally, ORF3a expression in HEK293 cells leads to lysosomal volume increase, mitochondrial damage, and accumulation of intracellular membranes, all alterations reverted by the N82W mutation.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region ORF3a
Standardized Encoding Gene ORF3a  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39905220
Title SARS-CoV-2 ORF3a accessory protein is a water-permeable channel that induces lysosome swelling
Author Michelucci A,Sforna L,Focaia R,Leonardi MV,Di Battista A,Rastelli G,Vespa S,Boncompagni S,Di Cristina M,Catacuzzeno L
Journal Communications biology
Journal Info 2025 Feb 4;8(1):170
Abstract ORF3a, the most abundantly expressed accessory protein of SARS-CoV-2, plays an essential role in virus egress by inactivating lysosomes through their deacidification. However, the mechanism underlying this process remains unclear. While seminal studies suggested ORF3a being a cation-selective channel (i.e., viroporin), recent works disproved this conclusion. To unravel the potential function of ORF3a, here we employed a multidisciplinary approach including patch-clamp electrophysiology, videoimaging, molecular dynamics (MD) simulations, and electron microscopy. Preliminary structural analyses and patch-clamp recordings in HEK293 cells rule out ORF3a functioning as either viroporin or proton (H(+)) channel. Conversely, videoimaging experiments demonstrate that ORF3a mediates the transmembrane transport of water. MD simulations identify the tetrameric assembly of ORF3a as the functional water transporter, with a putative selectivity filter for water permeation that includes two essential asparagines, N82 and N119. Consistent with this, N82L and N82W mutations abolish ORF3a-mediated water permeation. Finally, ORF3a expression in HEK293 cells leads to lysosomal volume increase, mitochondrial damage, and accumulation of intracellular membranes, all alterations reverted by the N82W mutation. We propose a novel function for ORF3a as a lysosomal water-permeable channel, essential for lysosome deacidification and inactivation, key steps to promote virus egress.
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.