دورية أكاديمية
SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
العنوان: | SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis |
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المؤلفون: | Saisai Guo, Xiaobo Lei, Yan Chang, Jianyuan Zhao, Jing Wang, Xiaojing Dong, Qian Liu, Zixiong Zhang, Lidan Wang, Dongrong Yi, Ling Ma, Quanjie Li, Yongxin Zhang, Jiwei Ding, Chen Liang, Xiaoyu Li, Fei Guo, Jianwei Wang, Shan Cen |
المصدر: | Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-12 (2022) |
بيانات النشر: | Nature Publishing Group, 2022. |
سنة النشر: | 2022 |
المجموعة: | LCC:Medicine LCC:Biology (General) |
مصطلحات موضوعية: | Medicine, Biology (General), QH301-705.5 |
الوصف: | Abstract The coronavirus disease 2019 (COVID-19) pandemic has devastated global health. Identifying key host factors essential for SARS-CoV-2 RNA replication is expected to unravel cellular targets for the development of broad-spectrum antiviral drugs which have been quested for the preparedness of future viral outbreaks. Here, we have identified host proteins that associate with nonstructural protein 12 (nsp12), the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 using a mass spectrometry (MS)-based proteomic approach. Among the candidate factors, CDK2 (Cyclin-dependent kinase 2), a member of cyclin-dependent kinases, interacts with nsp12 and causes its phosphorylation at T20, thus facilitating the assembly of the RdRp complex consisting of nsp12, nsp7 and nsp8 and promoting efficient synthesis of viral RNA. The crucial role of CDK2 in viral RdRp function is further supported by our observation that CDK2 inhibitors potently impair viral RNA synthesis and SARS-CoV-2 infection. Taken together, we have discovered CDK2 as a key host factor of SARS-CoV-2 RdRp complex, thus serving a promising target for the development of SARS-CoV-2 RdRp inhibitors. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2059-3635 |
Relation: | https://doaj.org/toc/2059-3635 |
DOI: | 10.1038/s41392-022-01239-w |
URL الوصول: | https://doaj.org/article/ffbcda39b3154046b3276edad622a296 |
رقم الأكسشن: | edsdoj.ffbcda39b3154046b3276edad622a296 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20593635 |
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DOI: | 10.1038/s41392-022-01239-w |