ArticleCell & bioscience2021
Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- SARS-CoV-2 ORF7a activates the endothelium to release von Willebrand factor that promotes thrombosis.Research and practice in thrombosis and haemostasis · 2025Article
- Article
- SARS-CoV-2 membrane protein induces neurodegeneration via affecting Golgi-mitochondria interaction.Translational neurodegeneration · 2024Article
- SARS-CoV-2 Nsp6-Omicron causes less damage to the Drosophila heart and mouse cardiomyocytes than ancestral Nsp6.Communications biology · 2024Article
- Mitochondria in COVID-19: from cellular and molecular perspective.Frontiers in physiology · 2024Review
- A comprehensive Drosophila resource to identify key functional interactions between SARS-CoV-2 factors and host proteins.Cell reports · 2023Article
- The Roles of Histone Lysine Methyltransferases in Heart Development and Disease.Journal of cardiovascular development and disease · 2023Review
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- SARS-CoV-2 Nsp6 damages Drosophila heart and mouse cardiomyocytes through MGA/MAX complex-mediated increased glycolysis.Communications biology · 2022Article
- Review
- Insights from a computational analysis of the SARS-CoV-2 Omicron variant: Host-pathogen interaction, pathogenicity, and possible drug therapeutics.Immunity, inflammation and disease · 2022Article
- Nucleopore Traffic Is Hindered by SARS-CoV-2 ORF6 Protein to Efficiently Suppress IFN-β and IL-6 Secretion.Viruses · 2022Article
- ACE and ACE2: insights fromHeliyon · 2021Review
- Understanding Individual SARS-CoV-2 Proteins for Targeted Drug Development against COVID-19.Molecular and cellular biology · 2021Review
- Entropy and Fractal Dimension Study of the TDP-43 Protein Low Complexity Domain Sequence in ALS Disease Severity and SARS-CoV-2 Gene Sequences in Virulence Variability.Entropy (Basel, Switzerland) · 2021Article
- Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2.Cell & bioscience · 2021Review
- Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor.Cell & bioscience · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSARS-CoV-2 causes COVID-19 with a widely diverse disease profile that affects many different tissues. The mechanisms underlying its pathogenicity in host organisms remain unclear. Animal models for studying the pathogenicity of SARS-CoV-2 proteins are lacking.
methodsUsing bioinformatic analysis, we found that 90% of the virus-host interactions involve human proteins conserved in Drosophila. Therefore, we generated a series of transgenic fly lines for individual SARS-CoV-2 genes, and used the Gal4-UAS system to express these viral genes in Drosophila to study their pathogenicity.
resultsWe found that the ubiquitous expression of Orf6, Nsp6 or Orf7a in Drosophila led to reduced viability and tissue defects, including reduced trachea branching as well as muscle deficits resulting in a "held-up" wing phenotype and poor climbing ability. Furthermore, muscles in these flies showed dramatically reduced mitochondria. Since Orf6 was found to interact with nucleopore proteins XPO1, we tested Selinexor, a drug that inhibits XPO1, and found that it could attenuate the Orf6-induced lethality and tissue-specific phenotypes observed in flies.
conclusionsOur study established Drosophila as a model for studying the function of SARS-CoV2 genes, identified Orf6 as a highly pathogenic protein in various tissues, and demonstrated the potential of Selinexor for inhibiting Orf6 toxicity using an in vivo animal model system.
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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.