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Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin.
Yin, Wanchao; Luan, Xiaodong; Li, Zhihai; Zhou, Ziwei; Wang, Qingxing; Gao, Minqi; Wang, Xiaoxi; Zhou, Fulai; Shi, Jingjing; You, Erli; Liu, Mingliang; Wang, Qingxia; Jiang, Yi; Jiang, Hualiang; Xiao, Gengfu; Zhang, Leike; Yu, Xuekui; Zhang, Shuyang; Eric Xu, H.
  • Yin W; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Luan X; School of Medicine, Tsinghua University, Haidian District, Beijing, China.
  • Li Z; Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
  • Zhou Z; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
  • Wang Q; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Gao M; Cryo-Electron Microscopy Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Wang X; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Zhou F; Cryo-Electron Microscopy Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Shi J; University of Chinese Academy of Sciences, Beijing, China.
  • You E; University of Chinese Academy of Sciences, Beijing, China.
  • Liu M; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Wang Q; WuxiBiortus Biosciences Co. Ltd, Jiangyin, China.
  • Jiang Y; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Jiang H; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Xiao G; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Zhang L; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Yu X; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Zhang S; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Eric Xu H; Cryo-Electron Microscopy Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Nat Struct Mol Biol ; 28(3): 319-325, 2021 03.
Article in English | MEDLINE | ID: covidwho-1118814
ABSTRACT
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 Å 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Suramin / Enzyme Inhibitors / Coronavirus RNA-Dependent RNA Polymerase Limits: Animals Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: S41594-021-00570-0

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Suramin / Enzyme Inhibitors / Coronavirus RNA-Dependent RNA Polymerase Limits: Animals Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: S41594-021-00570-0