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Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin

文献类型：期刊论文

作者Yin, Wanchao1; Luan, Xiaodong5,6,7; Li, Zhihai1,8; Zhou, Ziwei1,2,8; Wang, Qingxing2,3; Gao, Minqi4; Wang, Xiaoxi1; Zhou, Fulai1; Shi, Jingjing1; You, Erli1
刊名NATURE STRUCTURAL & MOLECULAR BIOLOGY
出版日期2021-03-05
页码21
ISSN号1545-9993
DOI10.1038/s41594-021-00570-0
通讯作者Zhang, Leike(zhangleike@wh.iov.cn) ; Yu, Xuekui(xkyu@simm.ac.cn) ; Zhang, Shuyang(shuyangzhang103@nrdrs.org) ; Eric Xu, H.(eric.xu@simm.ac.cn)
英文摘要The antiparasitic drug suramin directly inhibits SARS-CoV-2 RNA-dependent RNA polymerase by blocking binding of the RNA template-primer duplex and entry of nucleotide triphosphate to the catalytic site. The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and acts by blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for treatment of COVID-19. The 2.6 angstrom cryo-electron microscopy structure of the viral RdRp bound to suramin reveals two binding sites. One site directly blocks the binding of the RNA template strand and the other site clashes with the RNA primer strand near the RdRp catalytic site, thus inhibiting RdRp activity. Suramin blocks viral replication in Vero E6 cells, although the reasons underlying this effect are likely various. Our results provide a structural mechanism for a nonnucleotide inhibitor of the SARS-CoV-2 RdRp.
资助项目Shanghai Institute of Materia Medica ; National Key R&D Program of China[2020YFC0861000] ; CAMS Innovation Fund for Medical Sciences[2020-I2M-CoV19-001] ; Tsinghua University-Peking University Center for Life Sciences[045-160321001] ; National Key R&D Programs of China[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDB37030103] ; CAS Young Innovator Association award ; Chinese Academy of Sciences, Chinese Academy of Sciences[XDA12010317] ; Natural Science Foundation of Shanghai[18ZR1447700] ; National Natural Science Foundation of China[81903433] ; Shanghai Sailing Program[19YF1456800] ; Science and Technology Commission of Shanghai Municipal[20431900100] ; Jack Ma Foundation[2020-CMKYGG-05] ; Jack Ma Foundation[31770796] ; National Science and Technology Major Project[2018ZX09711002] ; K.C. Wong Education Foundation
WOS研究方向Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种英语
出版者NATURE RESEARCH
WOS记录号WOS:000625590000001
源URL[http://119.78.100.183/handle/2S10ELR8/295663]  
专题中国科学院上海药物研究所
通讯作者Zhang, Leike; Yu, Xuekui; Zhang, Shuyang; Eric Xu, H.
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, State Key Lab Virol, Wuhan, Hubei, Peoples R China
4.WuxiBiortus Biosci Co Ltd, Jiangyin, Peoples R China
5.Tsinghua Univ, Sch Med, Beijing, Peoples R China
6.Chinese Acad Med Sci & Peking Union Med Coll, Dept Cardiol, Peking Union Med Coll Hosp, Beijing, Peoples R China
7.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, Cryoelectron Microscopy Res Ctr, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Yin, Wanchao,Luan, Xiaodong,Li, Zhihai,et al. Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin[J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY,2021:21.
APA Yin, Wanchao.,Luan, Xiaodong.,Li, Zhihai.,Zhou, Ziwei.,Wang, Qingxing.,...&Eric Xu, H..(2021).Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin.NATURE STRUCTURAL & MOLECULAR BIOLOGY,21.
MLA Yin, Wanchao,et al."Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin".NATURE STRUCTURAL & MOLECULAR BIOLOGY (2021):21.

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来源：上海药物研究所

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