文献类型：期刊文献

英文题名：5-Iodotubercidin inhibits SARS-CoV-2 RNA synthesis

作者：Zhao, Jianyuan[1,2];Liu, Qian[2];Yi, Dongrong[1];Li, Quanjie[1];Guo, SaiSai[1];Ma, Ling[1];Zhang, Yongxin[1];Dong, Dongxin[2];Guo, Fei[3];Liu, Zhenlong[1,4];Wei, Tao[2];Li, Xiaoyu[1];Cen, Shan[1]

第一作者：Zhao, Jianyuan;赵江燕

通讯作者：Li, XY[1];Cen, S[1];Wei, T[2]

机构：[1]Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China;[2]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing, Peoples R China;[3]Chinese Acad Med Sci, Inst Pathogen Biol, Beijing, Peoples R China;[4]McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med,Div Expt Med, Montreal, PQ, Canada

第一机构：Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China

通讯机构：[1]corresponding author), Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China;[2]corresponding author), Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing, Peoples R China.|[1141726]北京联合大学生物化学工程学院;[11417]北京联合大学;[114172]北京联合大学应用文理学院;

年份：2022

卷号：198

外文期刊名：ANTIVIRAL RESEARCH

收录：;Scopus(收录号：2-s2.0-85123844280);WOS:【SCI-EXPANDED(收录号:WOS:000795700700005)】；

基金：Acknowledgments This work was supported by the National Key Research and Devel-opment Program of China (2018YFE0107600) , the National Natural Science Foundation of China (81772205 and 82104250) , CAMS Inno-vation Fund for Medical Sciences (2021-1-I2M-038 and 2021-I2M-1-030) and the Fundamental Research Funds for the Central Universities (33320200046) . This work was also supported by Beijing municipal Education Commission.

语种：英文

外文关键词：COVID-19; SARS-CoV-2; Nucleotide analogs; RdRp inhibitors

摘要：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-20Deoxyguanosine (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).