Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity

doi:10.1038/s41467-024-48503-x

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	Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity
	Wang, Shengjun 1,15; Ran, Wei 2; Sun, Lingyu 1; Fan, Qingchi 1; Zhao, Yuanqi 1,16; Wang, Bowen 3; Yang, Jinghong 2; He, Yuqi 1; Wu, Ying 1; Wang, Yuanyuan 4; Chen, Luoyi 1; Chuchuay, Arpaporn 1; You, Yuyu 1; Zhu, Xinhai 5; Wang, Xiaojuan 6; Chen, Ye 7; Wang, Yanqun 2; Chen, Yao-Qing 4; Yuan, Yanqiu 8; Zhao, Jincun2,9,10,11,12,13 ; Mao, Yang 1,14
	2024-05-16
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	15 期号:1
发表状态	已发表
DOI	10.1038/s41467-024-48503-x
摘要	The multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus.
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收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China["91853131","81872786","31971213","32271497","82025001"] ; National Key R&D Program of Ministry of Science and Technology of China[2021YFA1200903] ; Guangdong Provincial Key Laboratory of Drug Nonclinical Evaluation and Research[2018B030323024] ; Science and Technology Projects in Guangzhou[202103000029] ; Guangdong Basic and Applied Research Projects[2023B1515020040] ; Ministry of Agriculture, Food and Rural Affairs (MAFRA)[122012-2]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001310019300036
出版者	NATURE PORTFOLIO
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/427471
专题	免疫化学研究所免疫化学研究所_特聘教授组_赵金存组
通讯作者	Yuan, Yanqiu; Zhao, Jincun; Mao, Yang
作者单位	1.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou, Peoples R China 2.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou, Peoples R China 3.Northwest Univ, Coll Life Sci, Xian, Peoples R China 4.Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Shenzhen Campus, Shenzhen, Peoples R China 5.Sun Yat Sen Univ, Instrumental Anal Res Ctr, Guangzhou, Peoples R China 6.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Peoples R China 7.Fujian Agr & Forestry Univ, Coll Anim Sci, Key Lab Fujian Taiwan Anim Pathogen Biol, Fuzhou, Peoples R China 8.Sun Yat Sen Univ, Sch Pharmaceut Sci, State Key Lab Anti Infect Drug Discovery & Dev, Guangzhou, Peoples R China 9.Guangzhou Med Univ, Inst Infect Dis, Guangzhou Eighth Peoples Hosp, Guangzhou, Peoples R China 10.Bioisland, Guangzhou Lab, Guangzhou, Peoples R China 11.Southern Univ Sci & Technol, Affiliated Hosp 2, Sch Med, Shenzhen, Peoples R China 12.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Sch Life Sci & Technol, Shanghai, Peoples R China 13.Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Inst Hepatol, Shenzhen, Peoples R China 14.Guangdong Prov Key Lab Drug Nonclin Evaluat & Res, Guangzhou, Peoples R China 15.Univ Hlth & Rehabil Sci, Sch Hlth & Life Sci, Qingdao, Peoples R China 16.Foshan Inst Food & Drug Control, Foshan, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Wang, Shengjun,Ran, Wei,Sun, Lingyu,et al. Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity[J]. NATURE COMMUNICATIONS,2024,15(1).
APA	Wang, Shengjun.,Ran, Wei.,Sun, Lingyu.,Fan, Qingchi.,Zhao, Yuanqi.,...&Mao, Yang.(2024).Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.NATURE COMMUNICATIONS,15(1).
MLA	Wang, Shengjun,et al."Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity".NATURE COMMUNICATIONS 15.1(2024).