微生物与生化药学方向
赵建元
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时间:2024-02-27
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赵建元 免疫生物学室 副研究员 硕士生导师
教育背景及工作经历:
2022.10 –至今 中国医学科学院医药生物技术研究所 副研究员
2018.9 –2022.9 中国医学科学院医药生物技术研究所 助理研究员
2015.9-2018.7 北京协和医学院 微生物与生化药学,博士
主要研究方向:病毒学基础研究和抗病毒药物应用研究
专业研究领域:
主要从事病毒宿主相互作用研究,以及新型抗病毒药物靶点和药物的发现。近年来致力于将PROTAC技术应用于抗病毒药物研发,发现了国际上首个基于E3连接酶TRIM25的体内高效抗病毒PROTAC分子APL-16-5。先后主持国家自然科学基金面上项目和青年项目、北京市自然科学基金面上项目及抗病毒性传染病创新药物全国重点实验室开放课题等多项科研任务。在国内外学术期刊发表论文70余篇,其中近五年以第一作者(含共同第一)或通讯作者身份在Nature Communications、Signal Transduction and Targeted Therapy、Journal of Infection等权威期刊发表SCI收录论文13篇,影响因子10分以上者5篇。相关研究成果申请国家发明专利21项(其中12项已获授权),并提交国际PCT专利申请2项。现任中国药理学会呼吸药理专业委员会委员。曾获北京药理学会青年科学家论坛卓越奖(中文组第一名,2025)、中国药理学会高质量学术报告(2025)及优秀学术报告(2024)等荣誉,并于2021年获医药生物技术研究所“大村智-甄永苏青年科技奖”。
代表性论文:
1)Zhao J#, Wang J#, Pang X#, Liu Z, Li Q, Yi D, Zhang Y, Fang X, Zhang T, Zhou R, Zhang T, Guo Z, Liu W, Li X, Liang C, Deng T, Guo F*, Yu L*, Cen S*. An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA. Nat Commun. 2022 Apr 19;13(1):2079.
2)Guo S#, Lei X#, Chang Y#, Zhao J#, Wang J#, Dong X, Liu Q, Zhang Z, Wang L, Yi D, Ma L, Li Q, Zhang Y, Ding J, Liang C, Li X, Guo F*, Wang J*, Cen S*. SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis. Signal Transduct Target Ther. 2022 Dec 27;7(1):400. doi: 10.1038/s41392-022-01239-w. (#Co-first author)
3)Zhao J#, Liu Q#, Yi D#, Li Q, Guo S, Ma L, Zhang Y, Dong D, Guo F, Liu Z, Wei T*, Li X*, Cen S*. 5-Iodotubercidin inhibits SARS-CoV-2 RNA synthesis. Antiviral Res. 2022 Feb;198:105254.
4)Zhao J#, Zhang G#, Li Y#, Ma L, Yi D, Li Q, Shi Y, Guo S, Liu T, Wang Y, Li X, Wang Y, Tan W, Li J, Cen S. Discovery and optimization of phenazopyridine hydrochloride as novel SARS-CoV-2 RdRp inhibitors. Eur J Med Chem. 2025 Apr 15;288:117422. doi: 10.1016/j.ejmech.2025.117422. Epub 2025 Feb 20. PMID: 39999742.
5)Zhao J#, Guo S#, Yi D#, et al. A cell-based assay to discover inhibitors of SARS-CoV-2 RNA dependent RNA polymerase. Antiviral Res. 2021 Apr 21;190:105078. doi: 10.1016/j.antiviral.2021.105078.
6)Zhao J#, Zhang G#, Zhang Y#, et al. 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides: SARS-CoV-2 RNA-dependent RNA polymerase inhibitors. Antiviral Res. 2021 Nov 18:105209. doi: 10.1016/j.antiviral.2021.105209.
7)Zhao J#, Zhang Y#, Wang M#, et al. Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp. ACS Infect Dis. 2021 May 26. doi: 10.1021/acsinfecdis.1c00083.
8)Zhang G#, Zhao J#, Li Q#, et al. Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors. Eur J Med Chem, Volume 223, 5 November 2021, 113622 (#Co-first author)
9)Zhang G#, Wang M#, Zhao J#, Wang Y, Zhu M, Wang J, Cen S, Wang Y. Design, synthesis and in vitro anti-influenza A virus evaluation of novel quinazoline derivatives containing S-acetamide and NH-acetamide moieties at C-4. Eur J Med Chem. 2020 Nov 15;206:112706. (#Co-first author)
10)Pang X#, Zhao J#, Wang YJ, et al. Steroidal glycosides, homoisoflavanones and cinnamic acid derivatives from Polygonatum odoratum and their inhibitory effects against influenza A virus. Fitoterapia. 2020 Oct;146:104689. doi: 10.1016/j.fitote.2020.104689. (#Co-first author)
11)Ding J#, Zhao J#, Zhou J, Li X, Wu Y, Ge M, Cen S. Association of gene polymorphism of SDF1 (CXCR12) with susceptibility to HIV-1 infection and AIDS disease progression: A meta-analysis. PloS one, 2018,13(2), e0191930. (#Co-first author)
12)Zhao J , Zhao Y , Yang S , et al. Determination of Midazolam in Animal Tissues by Solid-Phase Extraction HPLC-MS/MS Method[J]. Asian Journal of Chemistry, 2014, 26(16):5235-5238. (#Co-first author)
13)Ding J# , Zhao J #, Yang Z# , et al. Microbial Natural Product Alternariol 5-O-Methyl Ether Inhibits HIV-1 Integration by Blocking Nuclear Import of the Pre-Integration Complex[J]. Viruses, 2017, 9(5):105. (#Co-first author)
14)Ding J# , Zhao J# , Sun L , et al. Citron kinase enhances ubiquitination of HIV-1 Gag protein and intracellular HIV-1 budding[J]. Archives of Virology, 2016, 161(9):1-8. (#Co-first author)
15)Wang J#, Zhang Y#, Li Q, Zhao J, Yi D, Ding J, Zhao F, Hu S, Zhou J, Deng T, Li X*, Guo F, Liang C, Cen S*. Influenza virus exploits an interferon-independent lncRNA to preserve viral RNA synthesis through stabilizing viral RNA polymerase PB1.Cell report, 2019, https://doi.org/10.1016/j.celrep.2019.05.036
16)Li Q#, Yi D#, Lei X#, Zhao J, Zhang Y, Cui X, Xiao X, Jiao T, Dong X, Zhao X, Zeng H, Liang C, Ren L, Guo F, Li X, Wang J, Cen S. Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase. Acta Pharm Sin B. 2021 Feb 15. doi: 10.1016/j.apsb.2021.02.011.
17)Wang M, Zhang G, Zhao J, Cheng N, Wang Y, Fu Y, Zheng Y, Wang J, Zhu M, Cen S, He J, Wang Y. Synthesis and antiviral activity of a series of novel quinoline derivatives as anti-RSV or anti-IAV agents. Eur J Med Chem. 2021 Mar 15;214:113208. doi: 10.1016/j.ejmech.2021.113208.
18)Zhang R, He W, Wang Y, Zhao J, Zhou R, Li L, He Y, Cen S, Yu L. New butyrolactone derivatives from the endophytic Fungus Talaromyces sp. CPCC 400783 of Reynoutria japonica Houtt. J Antibiot (Tokyo). 2021 Apr;74(4):225-232. doi: 10.1038/s41429-020-00388-w.
19)Ma L, Chen S, Wang Z, Guo S, Zhao J, Yi D, Li Q, Liu Z, Guo F, Li X, Jia P, Ding J, Liang C, Cen S. The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR. Virol Sin. 2021 Mar 15. doi: 10.1007/s12250-021-00363-1.
20)Fan Y, Zhang D, Tao X, Wang Y, Liu J, Li L, Zhao J, Yu L, He YP, Dai J, Tang Y. Biosynthetic Hypothesis-Guided Discovery and Total Syntheses of PKS-NRPS Hybrid Metabolites from Endophytic Fungus Periconia Species. Org Lett. 2019 Mar 15;21(6):1794-1798. doi: 10.1021/acs.orglett.9b00371.
21)Zhang D, Zhao J, Wang X, Zhao L, Liu H, Wei Y, Wang Y, You X, Cen S, Yu L*.Peniazaphilin A, a new azaphilone derivative produced by Penicillium sp. CPCC 400786.The Journal of antibiotics, 2018, 71(10), 905.
22)Pang X, Zhao J, Yu H, Yu L*, Wang T, Zhang Y, Gao X, Han L. Secoiridoid analogues from the fruits of Ligustrum lucidum and their inhibitory activities against influenza A virus. Bioorganic & medicinal chemistry letters, 2018, 28(9), 1516-1519.
23)Ding J , Ma L , Zhao J , et al. An integrative genomic analysis of transcriptional profiles identifies characteristic genes and patterns in HIV-infected long-term non-progressors and elite controllers[J]. Journal of Translational Medicine, 2019, 17(1).
24)Zhang GN, Li Q, Zhao J, Zhang X, Xu Z, Wang Y, Fu Y, Shan Q, Zheng Y, Wang J, Zhu M, Li Z, Cen S, He J, Wang Y. Design and synthesis of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides as novel dual inhibitors of respiratory syncytial virus and influenza virus A. Eur J Med Chem. 2020 Jan 15;186:111861. doi: 10.1016/j.ejmech.2019.111861.
25)Jing, W. , Wang, Y. , Rui, Z. , Zhao, J. , Zhang, Y. , & D Yi, et al. (2018). Host long noncoding rna lncrna-paan regulates the replication of influenza a virus. Viruses, 10(6), 330.
26)Qi X, Li X, Zhao J, He N, Li Y, Zhang T, Wang S, Yu L, Xie Y. GKK1032C, a new alkaloid compound from the endophytic fungus Penicillium sp. CPCC 400817 with activity against methicillin-resistant S. aureus. J Antibiot (Tokyo). 2019 Apr;72(4):237-240. doi: 10.1038/s41429-019-0144-5.
27)Pang X , Zhao J, Liu N , et al. Anthraquinone analogues with inhibitory activities against influenza a virus from Polygonatum odoratum[J]. Journal of Asian Natural Products Research, 2021 Aug;23(8):717-723.
28)Pang X , Zhao J, Fang X, et al. Metabolites from the Plant Endophytic Fungus Aspergillus sp. CPCC 400735 and Their Anti-HIV Activities[J]. Journal of Natural Products, 2017:2595.
29)Pang X, Zhao J, Fang X, et al. Surfactin derivatives from Micromonospora sp. CPCC 202787 and their anti-HIV activities[J]. Journal of Antibiotics, 2016.
授权专利:
1)一株曲霉菌及其应用,余利岩、庞旭、岑山、赵建元、张涛、方晓梅、刘红宇、苏静、张德武,专利号ZL 201610424586. 3,授权公告日:2019年07月12日。
2)聚酮在抑制HIV中的应用,余利岩、庞旭、岑山、赵建元、张涛、方晓梅、刘红宇、苏静、张德武,专利号ZL 201610425273.X,授权公告日:2019年07月12日。
3)聚酮在抑制流感病毒中的应用,余利岩、岑山、赵建元、庞旭、张涛、方晓梅、张永欣,专利号ZL201710077812.X,授权公告日:2019年12月31日。
4)一株曲霉菌的用途及由该曲霉菌制备的化合物及其用途,余利岩、庞旭、岑山、赵建元、张涛、方晓梅、刘红宇、苏静、张德武,ZL201910609383.5,授权公告日:2021年11月19日。
5)柯里拉京在抑制冠状病毒复制从而发挥抗冠状病毒药物功能中的应用。岑山、李泉洁、衣岽戎、赵建元、张永欣、李晓宇、刘振龙,专利号ZL202011083092.6,授权公告日:2021年9月17日。
6)盐酸非那吡啶的医药用途,岑山、王宇佳、吕凯、赵建元、郭赛赛、马铃,专利号ZL 202010123040.0,授权公告日:2021年9月7日。
7)含氮杂环甘草次酸衍生物及其制备方法和抗甲型流感病毒应用,孟庆国、赵风兰、张德武、赵若琳、刘智、赵建元、岑山、王嘉珍、邓建强、牟晓懂、王晓慧、刘丽、栾明珠、张晓凡、孙可微、唐航军、马颖,专利号ZL201911177679.0,授权公告日:2021年6月11日。
8)一种喹啉类化合物在制备抗冠状病毒抑制剂中的应用。岑山、赵建元、王玉成、王明华、张永欣。专利号ZL202011545756.6,授权公告日:2022年2月11日。
9)一种取代吲哚类化合物在制备抗冠状病毒抑制剂中的应用。岑山、赵建元、王玉成、张国宁、张永欣。专利号ZL202011540138.2,授权公告日:2022年2月11日。
10)含有环丙基骨架的化合物在制备治疗和/或预防冠状病毒感染药物中的应用,岑山、吕凯、刘明亮、赵建元,专利号ZL202110261343.3,授权公告日:2023年7月4日。
11)腺苷激酶抑制剂在制备抗冠状病毒制剂中的应用,岑山、赵建元、李晓宇、张永欣,专利号ZL202111222052.X,授权公告日:2023年7月4日。
12)余利岩,岑山,赵建元,庞旭,张涛,刘万仓,张涛。一种萘嵌苯酮类化合物及其应用,申请号CN202110905681.6,申请日:2021年8月6日,授权公告日:2025年1月10日。
13)一种萘嵌苯酮类化合物及其应用,余利岩、岑山、赵建元、庞旭、张涛、刘万仓、张涛,申请号CN202110905681.6,申请日:2021年8月6日
14)氯丙嗪在制备冠状病毒抑制剂中的应用,岑山、赵建元、任丽丽、魏涛、梅佳佳,申请号202310515271X,申请日:2023年5月9日
15)一种取代吲哚衍生物在制备治疗或预防流感的药物中的应用。岑山,赵建元,张国宁,王玉成,刘天福,申请号2023116222487,申请日:2023年11月30日
联系电话:010-63131011
电子邮箱:zhaojianyuan@imb.pumc.edu.cn