SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.
SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.
复制标题
SARS-COV-2劫持细胞激酶CDK2以促进病毒RNA合成。
DOI:
10.1038/s41392-022-01239-w
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发表时间:
2022-12-27
影响因子:
39.3
通讯作者:
Cen, Shan
中科院分区:
文献类型:
--
作者:
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
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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DOI:
10.1016/j.apsb.2021.02.011
发表时间:
2021-06
期刊:
Acta pharmaceutica Sinica. B
影响因子:
--
作者:
Li Q;Yi D;Lei X;Zhao J;Zhang Y;Cui X;Xiao X;Jiao T;Dong X;Zhao X;Zeng H;Liang C;Ren L;Guo F;Li X;Wang J;Cen S
通讯作者:
Cen S
影响因子:
14.9
作者:
te Velthuis AJ;Arnold JJ;Cameron CE;van den Worm SH;Snijder EJ
通讯作者:
Snijder EJ
影响因子:
14.9
作者:
Chen T;Ma J;Liu Y;Chen Z;Xiao N;Lu Y;Fu Y;Yang C;Li M;Wu S;Wang X;Li D;He F;Hermjakob H;Zhu Y
通讯作者:
Zhu Y
影响因子:
2.5
作者:
Kim, S. -J.;Kim, J. -H.;Oh, J. -W.
通讯作者:
Oh, J. -W.
影响因子:
14.9
作者:
te Velthuis AJ;van den Worm SH;Snijder EJ
通讯作者:
Snijder EJ