ReviewFrontiers in microbiology2022
Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19.
Review in Frontiers in microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 128 citations in OpenAlex.
- The accessory protein ORF3a hijacks the CLCC1 chloride channel to disrupt ER homeostasis in betacoronavirus pathogenesis.Cell discovery · 2026Article
- Circulating cholesterol fuels SARS-CoV-2 replication via ORF3a.EMBO reports · 2026Article
- ZDHHC18-Mediated Palmitoylation of ORF3a Promotes SARS-CoV-2 Pathogenesis by Antagonizing TRIM16-Mediated Ubiquitination and Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SARS-CoV-2 ORF3a suppresses host antiviral interferon responses by promoting STUB1-mediated PTEN proteasomal degradation.Journal of virology · 2026Article
- SARS-CoV-2 enhances lysosomal exocytosis and deacidifies lysosomes to facilitate viral release.mLife · 2026Article
- The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.Nature communications · 2026Article
- Redundant and distinct mechanisms suppress innate immune activation during SARS-CoV-2 infection.PLoS biology · 2026Article
- Distinct virus-derived circular RNA molecule influences host response during SARS-CoV-2 infection.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 Orf3a protein interaction mapping using unnatural amino acid incorporation.Protein engineering, design & selection : PEDS · 2026Article
- The structure and function of membrane protein in coronavirus infection and its applications in the development of vaccines and therapeutic drugs.Frontiers in microbiology · 2026Review
- ORF3 Depletion Attenuates SADS-CoV Virulence and Retains Partial Maternally Mediated Protection in Suckling Mice.Transboundary and emerging diseases · 2026Article
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- Ex vivo detection of SARS CoV 2 spike protein in human hair follicles and potential link to telogen effluvium.Scientific reports · 2025Article
- Porcine Epidemic Diarrhea-Virus-Induced Cell Death: Mechanistic Insights and Therapeutic Strategies.Veterinary sciences · 2025Review
- Article
- The SARS-CoV-2 envelope PDZ binding motif acts as a virulence factor disrupting host's epithelial cell-cell junctions.Cellular & molecular biology letters · 2025Article
- A Novel Toolkit of SARS-CoV-2 Sub-Genomic Replicons for Efficient Antiviral Screening.Viruses · 2025Article
- A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a.EBioMedicine · 2025Article
- Bid Protein: A Participant in the Apoptotic Network with Roles in Viral Infections.International journal of molecular sciences · 2025Review
- Quasi-species prevalence and clinical impact of evolving SARS-CoV-2 lineages in European COVID-19 cohorts, January 2020 to February 2022.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2025Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The ongoing SARS-CoV-2 pandemic has shocked the world due to its persistence, COVID-19-related morbidity and mortality, and the high mutability of the virus. One of the major concerns is the emergence of new viral variants that may increase viral transmission and disease severity. In addition to mutations of spike protein, mutations of viral proteins that affect virulence, such as ORF3a, also must be considered. The purpose of this article is to review the current literature on ORF3a, to summarize the molecular actions of SARS-CoV-2 ORF3a, and its role in viral pathogenesis and COVID-19. ORF3a is a polymorphic, multifunctional viral protein that is specific to SARS-CoV/SARS-CoV-2. It was acquired from β-CoV lineage and likely originated from bats through viral evolution. SARS-CoV-2 ORF3a is a viroporin that interferes with ion channel activities in host plasma and endomembranes. It is likely a virion-associated protein that exerts its effect on the viral life cycle during viral entry through endocytosis, endomembrane-associated viral transcription and replication, and viral release through exocytosis. ORF3a induces cellular innate and pro-inflammatory immune responses that can trigger a cytokine storm, especially under hypoxic conditions, by activating NLRP3 inflammasomes, HMGB1, and HIF-1α to promote the production of pro-inflammatory cytokines and chemokines. ORF3a induces cell death through apoptosis, necrosis, and pyroptosis, which leads to tissue damage that affects the severity of COVID-19. ORF3a continues to evolve along with spike and other viral proteins to adapt in the human cellular environment. How the emerging ORF3a mutations alter the function of SARS-CoV-2 ORF3a and its role in viral pathogenesis and COVID-19 is largely unknown. This review provides an in-depth analysis of ORF3a protein's structure, origin, evolution, and mutant variants, and how these characteristics affect its functional role in viral pathogenesis and COVID-19.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.