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SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis

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 vi...

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Autores principales: Guo, Saisai, Lei, Xiaobo, Chang, Yan, Zhao, Jianyuan, Wang, Jing, Dong, Xiaojing, Liu, Qian, Zhang, Zixiong, Wang, Lidan, Yi, Dongrong, Ma, Ling, Li, Quanjie, Zhang, Yongxin, Ding, Jiwei, Liang, Chen, Li, Xiaoyu, Guo, Fei, Wang, Jianwei, Cen, Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793359/
https://www.ncbi.nlm.nih.gov/pubmed/36575184
http://dx.doi.org/10.1038/s41392-022-01239-w
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author Guo, Saisai
Lei, Xiaobo
Chang, Yan
Zhao, Jianyuan
Wang, Jing
Dong, Xiaojing
Liu, Qian
Zhang, Zixiong
Wang, Lidan
Yi, Dongrong
Ma, Ling
Li, Quanjie
Zhang, Yongxin
Ding, Jiwei
Liang, Chen
Li, Xiaoyu
Guo, Fei
Wang, Jianwei
Cen, Shan
author_facet Guo, Saisai
Lei, Xiaobo
Chang, Yan
Zhao, Jianyuan
Wang, Jing
Dong, Xiaojing
Liu, Qian
Zhang, Zixiong
Wang, Lidan
Yi, Dongrong
Ma, Ling
Li, Quanjie
Zhang, Yongxin
Ding, Jiwei
Liang, Chen
Li, Xiaoyu
Guo, Fei
Wang, Jianwei
Cen, Shan
author_sort Guo, Saisai
collection PubMed
description 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.
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spelling pubmed-97933592022-12-27 SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis Guo, Saisai Lei, Xiaobo Chang, Yan Zhao, Jianyuan Wang, Jing Dong, Xiaojing Liu, Qian Zhang, Zixiong Wang, Lidan Yi, Dongrong Ma, Ling Li, Quanjie Zhang, Yongxin Ding, Jiwei Liang, Chen Li, Xiaoyu Guo, Fei Wang, Jianwei Cen, Shan Signal Transduct Target Ther Article 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. Nature Publishing Group UK 2022-12-27 /pmc/articles/PMC9793359/ /pubmed/36575184 http://dx.doi.org/10.1038/s41392-022-01239-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Guo, Saisai
Lei, Xiaobo
Chang, Yan
Zhao, Jianyuan
Wang, Jing
Dong, Xiaojing
Liu, Qian
Zhang, Zixiong
Wang, Lidan
Yi, Dongrong
Ma, Ling
Li, Quanjie
Zhang, Yongxin
Ding, Jiwei
Liang, Chen
Li, Xiaoyu
Guo, Fei
Wang, Jianwei
Cen, Shan
SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
title SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
title_full SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
title_fullStr SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
title_full_unstemmed SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
title_short SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis
title_sort sars-cov-2 hijacks cellular kinase cdk2 to promote viral rna synthesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793359/
https://www.ncbi.nlm.nih.gov/pubmed/36575184
http://dx.doi.org/10.1038/s41392-022-01239-w
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