A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors

doi:10.1016/j.cell.2022.09.037

	A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors
	Yan, Liming 1; Huang, Yucen 1,3; Ge, Ji 1,2; Liu, Zhenyu 1,4,5; Lu, Pengchi 6; Huang, Bo 7; Gao, Shan 1; Wang, Junbo 1; Tan, Liping 1; Ye, Sihan 1; Yu, Fengxi 3; Lan, Weiqi4,5 ; Xu, Shiya 1; Zhou, Feng 7; Shi, Lei 7; Guddat, Luke W.8; Gao, Yan4,5 ; Rao, Zihe1,2,4,5,9,10,11 ; Lou, Zhiyong 1
	2022-11-10
发表期刊	CELL (IF:45.5[JCR-2023],49.0[5-Year])
ISSN	0092-8674
EISSN	1097-4172
卷号	185 期号:23
发表状态	已发表
DOI	10.1016/j.cell.2022.09.037
摘要	Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mecha-nism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket"in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophos-phate, reasoning an "induce-and-lock"mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.
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收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China["32188101","U20A20135"] ; National Program on Key Research Project of China["2020YFA0707500","2017YFC0840300"]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000900775500002
出版者	CELL PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/268675
专题	免疫化学研究所_特聘教授组_饶子和组生命科学与技术学院生命科学与技术学院_博士生
通讯作者	Gao, Yan; Rao, Zihe; Lou, Zhiyong
作者单位	1.Tsinghua Univ, Sch Med, MOE Key Lab Prot Sci, Beijing, Peoples R China 2.Guangzhou Lab, Innovat Ctr Pathogen Res, Guangzhou, Peoples R China 3.Peking Univ, Tsinghua Univ Peking Univ Joint Ctr Life Sci, Sch Life Sci, Beijing, Peoples R China 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 6.UCL, Div Biosci, London, England 7.Beijing StoneWise Technol Co Ltd, Beijing, Peoples R China 8.Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Australia 9.Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin, Peoples R China 10.Nankai Univ, Coll Pharm, Tianjin, Peoples R China 11.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing, Peoples R China
通讯作者单位	免疫化学研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Yan, Liming,Huang, Yucen,Ge, Ji,et al. A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors[J]. CELL,2022,185(23).
APA	Yan, Liming.,Huang, Yucen.,Ge, Ji.,Liu, Zhenyu.,Lu, Pengchi.,...&Lou, Zhiyong.(2022).A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.CELL,185(23).
MLA	Yan, Liming,et al."A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors".CELL 185.23(2022).