#NSP4
-Chromatin remodeling: Reshapes chromatin to expose or conceal genes for transcription.
-Non-coding RNAs (ncRNAs): Regulates gene expression at the post-transcriptional level.
- Viral strategies to manipulate the host epigenome
-Viruses interact with host proteins involved in epigenetic regulation,
October 21, 2025 at 6:56 AM
A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription journals.asm.org/doi/10.1128/...
A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription | Journal of Virology
Coronaviruses, like many other positive-sense single-stranded RNA viruses, rely on intracellular membrane remodeling to create a protected environment for efficient replication to occur. The resulting double membrane vesicles (DMVs) have characteristic pores formed from the non-structural viral proteins nsp3 and nsp4, while enzymes responsible for RNA replication, including the polymerase nsp12, are contained inside. Recent structural work has elucidated the nature of the pores, but how the polymerase and other viral proteins are recruited to the DMV represents a major gap in our current knowledge. Here we present a novel, step-by-step structural model of how the pores initially form from the uncleaved polyprotein, how protease activity is initiated, and how the viral replication machinery is trapped within the DMV.
journals.asm.org
October 8, 2025 at 1:55 PM
Though the full mutational pattern is very diverse, its strongest & most distinctive aspects are three:

#1. Extraordinarily high rate of E mutations
#2. Specific mutations in NSP4
#3. A marked *absence* of spike RBD, NTD, & especially RBM mutations
11/
September 2, 2025 at 3:16 AM
A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription https://www.biorxiv.org/content/10.1101/2025.04.10.648184v1
April 12, 2025 at 4:19 AM
A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription https://www.biorxiv.org/content/10.1101/2025.04.10.648184v1
April 12, 2025 at 4:19 AM
Interestingly, B.1.637 is the only lineage with ORF1a:K3142E (another NSP4 mutation), which is *also* in this Kazakhstan dog sequence. Outside of B.1.637, ORF1a:K3142E is extremely rare, and occurred almost exclusively early in the pandemic. 16/
April 10, 2025 at 12:48 AM
One of our top mutations is actually NSP4 T492I, which was shown to improve protein cleavage and viral replication (see Lin et al. here). More generally, nearly all our top mutations are well-supported by experiments.

www.cell.com/cell-host-mi...
The NSP4 T492I mutation increases SARS-CoV-2 infectivity by altering non-structural protein cleavage
Lin et al. demonstrate that the NSP4 T492I substitution associates with the increased infectivity, transmissibility, and attenuated pathogenicity observed in recent SARS-CoV-2 variants, including Delt...
www.cell.com
January 31, 2025 at 10:00 PM
NSP4 protein in rotavirus is found crucial for infection severity by disrupting calcium signals. This breakthrough could pave the way for innovative treatments for rotavirus infections.
Unraveling Rotavirus: How NSP4 Influences Disease Severity
NSP4 protein in rotavirus is found crucial for infection severity by disrupting calcium signals. This breakthrough could pave the way for innovative treatments for rotavirus infections.
www.science-tldr.com
January 21, 2025 at 1:53 AM
Rotavirüs proteininin mide ve bağırsak hastalıklarındaki şiddetindeki rolü ortaya kondu. NSP4 proteini, kalsiyum sinyalini bozarak rotavirüs şiddetini artırıyor ve yeni tedavi stratejileri için bilgiler sunulmuş.
Rotavirus protein NSP4 manipulates gastrointestinal disease severity
Researchers at Baylor College of Medicine and collaborating institutions have improved our understanding of how rotavirus, the most common cause of acute...
www.bcm.edu
January 20, 2025 at 1:49 PM
Houston researchers found that rotavirus protein NSP4 disrupts cell calcium, spreading signals to uninfected cells and worsening disease.

Similar to SARS-CoV-2’s E protein.

www.science.org/doi/10.1126/...
Viroporin activity is necessary for intercellular calcium signals that contribute to viral pathogenesis
The NSP4 viroporin initiates an innate immune response and intercellular calcium waves that contribute to pathogenesis.
www.science.org
January 18, 2025 at 11:22 PM
Rotavirus protein NSP4 disrupts calcium signaling, influencing disease severity by affecting both infected and nearby uninfected cells. This insight could inform new strategies for treatment or prevention. doi.org/g82cqq
Rotavirus protein NSP4 manipulates calcium signaling, affecting disease outcomes
Researchers at Baylor College of Medicine and collaborating institutions have improved our understanding of how rotavirus, the most common cause of acute gastroenteritis in children, makes people sick.
medicalxpress.com
January 18, 2025 at 11:47 AM
SARS-CoV-2 proteins NSP3 and NSP4 form double-membrane vesicles for viral replication.

NSP3 anchors key components while NSP4 controls vesicle numbers.

Together with NSP12, they build the virus’s replication hub.

rupress.org/jcb/article-...
SARS-CoV-2 NSP3/4 control formation of replication organelle and recruitment of RNA polymerase NSP12
The NSP3/4/12 axis in β-coronaviruses orchestrates the formation of double-membrane vesicles (DMVs) and the assembly of replication organelles by utilizing
rupress.org
December 31, 2024 at 5:50 PM
Genomic analysis of DS-1-like human rotavirus A strains uncovers genetic relatedness of NSP4 gene with animal strains in Manhiça District, Southern Mozambique https://pubmed.ncbi.nlm.nih.gov/39730435/
December 29, 2024 at 9:12 AM
Interesting tidbit: in chronics there’s a very tight connection between mutations at E:5-42 (esp ∆V14 & T30I) & a region of NSP4 (ORF1a:3049-3089 plus—oddly—ORF1a:2972).

*All* S:L1186F chronics have ≥1 mut at E:5-36 & 8/11 have ≥1 in the NSP4 region.
31/64
December 23, 2024 at 6:09 PM
SARS-CoV-2 protein Nsp4 disrupts the endoplasmic reticulum (ER) in host cells to help form double-membrane vesicles for viral replication.

Study in yeast and human cells shows these disruptions bypass usual stress pathways but involve ESCRT proteins.

www.biorxiv.org/content/10.1...
Orchestration of SARS-CoV-2 Nsp4 and host-cell ESCRT proteins induces morphological changes of the endoplasmic reticulum
Upon entry into the host cell, the non-structural proteins 3, 4, and 6 (Nsp3, Nsp 4, and Nsp6) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate the formation of double-membra...
www.biorxiv.org
December 11, 2024 at 8:51 PM
University of California Study Finds That SARS-CoV-2 NSP4 Protein Alters Endoplasmic Reticulum Structure

www.thailandmedical.news/news/univers...
University of California Study Finds That SARS-CoV-2 NSP4 Protein Alters Endoplasmic Reticulum Structure - Thailand Medical News
www.thailandmedical.news
December 11, 2024 at 1:39 AM
Orchestration of SARS-CoV-2 Nsp4 and host-cell ESCRT proteins induces morphological changes of the endoplasmic reticulum https://www.biorxiv.org/content/10.1101/2024.12.08.627411v1
December 10, 2024 at 9:30 AM
Orchestration of SARS-CoV-2 Nsp4 and host-cell ESCRT proteins induces morphological changes of the endoplasmic reticulum https://www.biorxiv.org/content/10.1101/2024.12.08.627411v1
December 10, 2024 at 9:30 AM
can you ask criminal ed holmes why he refuses to publish the full GX_ZC45r-CoV genome even though it is one of the closest known CoVs to SARS-CoV-2 (partial NSP4 region ML tree shown)?
December 8, 2024 at 2:41 AM
can you ask criminal ed holmes why he refuses to publish the full GX_ZC45r-CoV genome even though it is one of the closest known CoVs to SARS-CoV-2 (partial NSP4 region ML tree shown)?
November 26, 2024 at 11:58 AM
Can you ask why fasteddie refuses to publish the full GX_ZC45r-CoV genome even though it is one of the closest known CoVs to SARS-CoV-2 (partial NSP4 region ML tree shown)?
November 19, 2024 at 3:28 AM
pGBW-m4134196
Depositor: Ginkgo Bioworks
Purpose: Mammalian expression plasmid for SARS-CoV-2 nsp4

www.addgene.org/152506/
September 20, 2024 at 8:00 PM