ArticleCell & bioscience2021
Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor.
Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Defining the Clinicoradiologic Syndrome of SARS-CoV-2 Acute Necrotizing Encephalopathy: A Systematic Review and 3 New Pediatric CasesNeurology(R) neuroimmunology & neuroinflammation · 2024Pooled it
- A P3' methionine-to-phenylalanine substitution in the NSP6-7 substrate peptide alters SARS-CoV-2 MThe Journal of biological chemistry · 2026Article
- Review
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- NRF2 activators and the inhibitor of nuclear export, selinexor, restrict coronaviruses by targeting a network involving ACE2, TMPRSS2, and XPO1 through an NRF2-independent mechanism.Communications biology · 2026Article
- Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins.Scientific reports · 2025Article
- Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.PLoS pathogens · 2025Article
- SARS-CoV-2 ORF7a activates the endothelium to release von Willebrand factor that promotes thrombosis.Research and practice in thrombosis and haemostasis · 2025Article
- Subcellular localization of SARS-CoV-2 E and 3a proteins along the secretory pathway.Journal of molecular histology · 2025Article
- Coupling of SARS-CoV-2 to Amyloid Fibrils and Liquid-Liquid Phase Separation.Current protein & peptide science · 2025Review
- Immuno-epigenetic paradigms in coronavirus infection.Frontiers in immunology · 2025Review
- SARS-CoV-2 Nsp6-Omicron causes less damage to the Drosophila heart and mouse cardiomyocytes than ancestral Nsp6.Communications biology · 2024Article
- SARS-CoV-2 NSP6 reduces autophagosome size and affects viral replication via sigma-1 receptor.Journal of virology · 2024Article
- Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies.Communications biology · 2024Article
- The emerging role of SARS-CoV-2 nonstructural protein 1 (nsp1) in epigenetic regulation of host gene expression.FEMS microbiology reviews · 2024Review
- Comparative Atlas of SARS-CoV-2 Substitution Mutations: A Focus on Iranian Strains Amidst Global Trends.Viruses · 2024Article
- A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.Journal of biomedical science · 2024Review
- SARS-CoV-2 Protein Nsp9 Is Involved in Viral Evasion through Interactions with Innate Immune Pathways.ACS omega · 2024Article
- Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSARS-CoV-2 causes COVID-19 which has a widely diverse disease profile. The mechanisms underlying its pathogenicity remain unclear. We set out to identify the SARS-CoV-2 pathogenic proteins that through host interactions cause the cellular damages underlying COVID-19 symptomatology.
methodsWe examined each of the individual SARS-CoV-2 proteins for their cytotoxicity in HEK 293 T cells and their subcellular localization in COS-7 cells. We also used Mass-Spec Affinity purification to identify the host proteins interacting with SARS-CoV-2 Orf6 protein and tested a drug that could inhibit a specific Orf6 and host protein interaction.
resultsWe found that Orf6, Nsp6 and Orf7a induced the highest toxicity when over-expressed in human 293 T cells. All three proteins showed membrane localization in COS-7 cells. We focused on Orf6, which was most cytotoxic and localized to the endoplasmic reticulum, autophagosome and lysosomal membranes. Proteomics revealed Orf6 interacts with nucleopore proteins (RAE1, XPO1, RANBP2 and nucleoporins). Treatment with Selinexor, an FDA-approved inhibitor for XPO1, attenuated Orf6-induced cellular toxicity in human 293 T cells.
conclusionsOur study revealed Orf6 as a highly pathogenic protein from the SARS-CoV-2 genome, identified its key host interacting proteins, and Selinexor as a drug candidate for directly targeting Orf6 host protein interaction that leads to cytotoxicity.
Identifiers
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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.