ArticleCell discovery2021
The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes.
Article in Cell discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 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.
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Who cites it
171 citing papers in PubMed, 234 citations in OpenAlex.
- Intermittent fasting and a no-sugar diet for Long COVID symptoms: a randomized crossover trial.Scientific reports · 2025Trial
- VPS33A and VPS18 orchestrate porcine epidemic diarrhea virus replication by modulating autophagic flux.Virulence · 2026Article
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- The accessory protein ORF3a hijacks the CLCC1 chloride channel to disrupt ER homeostasis in betacoronavirus pathogenesis.Cell discovery · 2026Article
- SARS-CoV-2 Delta variant-specific ORF3a mutations destabilize lysosomal homeostasis to trigger lysosomal damage-mediated cell death.Communications biology · 2026Article
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.Cell reports · 2026Article
- RNF26 bridges ER stress and autophagy in the clearance of MERS envelope protein.Virologica Sinica · 2026Article
- Review
- The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.Nature communications · 2026Article
- SARS-CoV-2 Nsp1 suppresses the canonical NF-κB pathway by promoting ubiquitin-dependent degradation of TAK1 kinase.PLoS pathogens · 2026Article
- ORF3 protein of porcine circovirus type 2 induced RIPK3 phosphorylation-driven autophagy to promote viral replication.Scientific reports · 2026Article
- Poxvirus A52 protein subverts autophagy flux by blocking autophagosome-lysosome fusion to promote viral replication.PLoS pathogens · 2026Article
- Botulinum toxin-induced masseter muscle atrophy is associated with impaired autophagic flux without signs of apoptosis in mice.Cell death discovery · 2026Article
- Role of autophagy in antiviral innate immunity.Cellular & molecular biology letters · 2026Review
- Article
- Critical Roles and Molecular Mechanisms of Chaperone-Mediated Autophagy in Infections.International journal of molecular sciences · 2026Review
- SARS-CoV-2 Orf3a protein interaction mapping using unnatural amino acid incorporation.Protein engineering, design & selection : PEDS · 2026Article
- Dual-function cytokines as modulators of autophagy: reprogramming inflammatory resolution in severe COVID-19.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Tetrandrine-driven autophagy suppresses SARS-CoV-2 replication by modulating cholesterol and IGF signaling pathways.Cell death discovery · 2026Article
- Fragile mitophagy in long COVID: a proposed recovery-failure endotype for post-exertional malaise.Frontiers in medicine · 2026Article
111 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
8 authors at 5 institutions in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 pandemic. How SARS-CoV-2 regulates cellular responses to escape clearance by host cells is unknown. Autophagy is an intracellular lysosomal degradation pathway for the clearance of various cargoes, including viruses. Here, we systematically screened 28 viral proteins of SARS-CoV-2 and identified that ORF3a strongly inhibited autophagic flux by blocking the fusion of autophagosomes with lysosomes. ORF3a colocalized with lysosomes and interacted with VPS39, a component of the homotypic fusion and protein sorting (HOPS) complex. The ORF3a-VPS39 interaction prohibited the binding of HOPS with RAB7, which prevented the assembly of fusion machinery, leading to the accumulation of unfused autophagosomes. These results indicated the potential mechanism by which SARS-CoV-2 escapes degradation; that is, the virus interferes with autophagosome-lysosome fusion. Furthermore, our findings will facilitate strategies targeting autophagy for conferring potential protection against the spread of SARS-CoV-2.
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.