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5-Iodotubercidin inhibits SARS-CoV-2 RNA synthesis.
Zhao, Jianyuan; Liu, Qian; Yi, Dongrong; Li, Quanjie; Guo, SaiSai; Ma, Ling; Zhang, Yongxin; Dong, Dongxin; Guo, Fei; Liu, Zhenlong; Wei, Tao; Li, Xiaoyu; Cen, Shan.
  • Zhao J; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China; Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, China.
  • Liu Q; Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, China.
  • Yi D; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
  • Li Q; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
  • Guo S; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
  • Ma L; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
  • Zhang Y; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
  • Dong D; Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, China.
  • Guo F; Institute of Pathogen Biology, Chinese Academy of Medical Science, Beijing, China.
  • Liu Z; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China; Lady Davis Institute for Medical Research, Jewish General Hospital, Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.
  • Wei T; Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, China. Electronic address: weitao@buu.edu.cn.
  • Li X; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China. Electronic address: lixiaoyu@imb.pumc.edu.cn.
  • Cen S; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China. Electronic address: shancen@imb.pumc.edu.cn.
Antiviral Res ; 198: 105254, 2022 02.
Article in English | MEDLINE | ID: covidwho-1654045
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid global emergence of SARS-CoV-2 highlights the importance and urgency for potential drugs to control the pandemic. The functional importance of RNA-dependent RNA polymerase (RdRp) in the viral life cycle, combined with structural conservation and absence of closely related homologs in humans, makes it an attractive target for designing antiviral drugs. Nucleos(t)ide analogs (NAs) are still the most promising broad-spectrum class of viral RdRp inhibitors. In this study, using our previously developed cell-based SARS-CoV-2 RdRp report system, we screened 134 compounds in the Selleckchemicals NAs library. Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp. Among these four compounds, 5-Iodotubercidin exhibited the strongest inhibition upon SARS-CoV-2 RdRp, and was resistant to viral exoribonuclease activity, thus presenting the best antiviral activity against coronavirus from a different genus. Further study showed that the RdRp inhibitory activity of 5-Iodotubercidin is closely related to its capacity to inhibit adenosine kinase (ADK).
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Tubercidin / Nucleic Acid Synthesis Inhibitors / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Traditional medicine Limits: Humans Language: English Journal: Antiviral Res Year: 2022 Document Type: Article Affiliation country: J.antiviral.2022.105254

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Tubercidin / Nucleic Acid Synthesis Inhibitors / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Traditional medicine Limits: Humans Language: English Journal: Antiviral Res Year: 2022 Document Type: Article Affiliation country: J.antiviral.2022.105254