Academic Journal
Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor
| العنوان: | Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor |
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| المؤلفون: | Jin-Gu Lee, Weiliang Huang, Hangnoh Lee, Joyce van de Leemput, Maureen A. Kane, Zhe Han |
| المصدر: | Cell & Bioscience, Vol 11, Iss 1, Pp 1-12 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biotechnology LCC:Biology (General) LCC:Biochemistry |
| مصطلحات موضوعية: | Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5, Biochemistry, QD415-436 |
| الوصف: | Abstract Background SARS-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. Methods We 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. Results We 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. Conclusions Our 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-3701 |
| Relation: | https://doaj.org/toc/2045-3701 |
| DOI: | 10.1186/s13578-021-00568-7 |
| URL الوصول: | https://doaj.org/article/56b38ae7fa894eb195fa10ac7eac0446 |
| رقم الانضمام: | edsdoj.56b38ae7fa894eb195fa10ac7eac0446 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20453701 |
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| DOI: | 10.1186/s13578-021-00568-7 |