工作及教育经历

2009-2013 清华大学医学院生物学专业 博士

2013-2016 清华大学医学院 博士后

2016-2022 清华大学医学院 助理研究员

2022-2024 清华大学医学院 副研究员 

2024-至今 清华大学基础医学院 副研究员

研究领域

冠状病毒是目前已知最大的基因组RNA病毒，其编码16个非结构蛋白nsp1~nsp16，这些非结构蛋白组成转录复制复合体RTC完成基因组和亚基因组的合成，具体蛋白元件包含了聚合酶、引物酶、单链结合蛋白、激活蛋白、解旋酶、复制校正酶和甲基转移酶等，这些蛋白元件负责病毒转录复制的核心过程，涵盖了众多抗病毒药物设计的关键靶点。课题组主要通过结构生物学、生物化学和病毒学手段，发现新靶点和新机制，研发高效、广谱的抗病毒药物。

科学贡献

解析新冠病毒核心复制酶结构（Science 2020），提出瑞德西韦等核苷药物抑制新冠病毒的分子机制；揭示新冠病毒解旋酶和聚合酶偶联的RNA复制延伸模型（Nat Commun 2021）；发现冠状病毒帽子合成的中间态（Cell 2021）；解析了冠状病毒加帽与校正酶复合物结构（Cell 2021），首次提出新冠病毒核苷类药物的逃逸分子机制；明确聚合酶催化nsp9介导的帽子合成机制(Cell 2022），发现了全新的抗病毒药物靶点NiRAN。

荣誉奖励

2023 钟南山青年科技创新奖

2021 中国科学十大进展

2021 中国生命科学十大进展

2021 教育部青年长江学者

代表性论文

1.Yan, Liming^#., Huang, Y^#., Ge, J^#., Liu, Z^#., Lu, P., Huang, B., Gao, S., Wang, J., Tan, L., Ye, S., Yu, F., Lan, W., Xu, S., Zhou, F., Shi, L., Guddat, L. W., Gao, Y*., Rao, Z*., and Lou, Z*. (2022). A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors. Cell 185, 4347-4360.e4317.

2.Yan, Liming^#., Yang, Y^#., Li, M^#., Zhang, Y^#., Zheng, L^#., Ge, J^#., Huang, Y. C^#., Liu, Z^#., Wang, T., Gao, S., Zhang, R., Huang, Y. Y., Guddat, L. W., Gao, Y*., Rao, Z*., and Lou, Z*. (2021b). Coupling of N7-methyltransferase and 3'-5' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading. Cell 184, 3474-3485 e3411.

3.Yan, Liming^#., Ge, J^#., Zheng, L^#., Zhang, Y., Gao, Y., Wang, T., Huang, Y., Yang, Y., Gao, S., Li, M., Liu, Z., Wang, H., Li, Y., Chen, Y., Guddat, L. W., Wang, Q., Rao, Z*., and Lou, Z*. (2021a). Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex Reveals an Intermediate State in Cap Synthesis. Cell 184, 184-193 e110.

4.Yan, Liming^#., Zhang, Y^#., Ge, J., Zheng, L., Gao, Y., Wang, T., Jia, Z., Wang, H., Huang, Y., Li, M., Wang, Q., Rao, Z*., and Lou, Z*. (2020). Architecture of a SARS-CoV-2 mini replication and transcription complex. Nat Commun 11, 5874.

5.Gao, Y^#., Yan, Liming^#., Huang, Y^#., Liu, F^#., Zhao, Y., Cao, L., Wang, T., Sun, Q., Ming, Z., Zhang, L., Ge, J., Zheng, L., Zhang, Y., Wang, H., Zhu, Y., Zhu, C., Hu, T., Hua, T., Zhang, B., Yang, X., Li, J., Yang, H., Liu, Z., Xu, W., Guddat, L. W., Wang, Q*., Lou, Z*., and Rao, Z*. (2020). Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368, 779-782.

6.Yan, Liming^#., Qi, Y^#., Ricketson, D^#., Li, L., Subramanian, K., Zhao, J., Yu, C., Wu, L., Sarsam, R., Wong, M., Lou, Z., Rao, Z*., Nunnari, J*., and Hu, J*. (2020). Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1. Proceedings of the National Academy of Sciences of the United States of America 117, 4061-4070.

7.Yu, C^#., Zhao, J^#., Yan, Liming^#., Qi, Y., Guo, X., Lou, Z., Hu, J*., and Rao, Z. (2020). Structural insights into G domain dimerization and pathogenic mutation of OPA1. J Cell Biol 219.

8.Jia, Z^#., Yan, Liming^#., Ren, Z., Wu, L., Wang, J., Guo, J., Zheng, L., Ming, Z., Zhang, L., Lou, Z., and Rao, Z*. (2019). Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic acids research 47, 6538-6550.

9.Yan, Liming^#., Qi, Y. B^#., Huang, X. F^#., Yu, C. T^#., Lan, L., Guo, X. Y., Rao, Z. H., Hu, J. J*., and Lou, Z. Y*. (2018). Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion. Nature structural & molecular biology 25, 233-+.

10.Yan, Liming^#., Sun, S^#., Wang, W., Shi, J., Hu, X., Wang, S., Su, D., Rao, Z., Hu, J*., and Lou, Z*. (2015). Structures of the yeast dynamin-like GTPase Sey1p provide insight into homotypic ER fusion. J Cell Biol 210, 961-972.

11.Qi, Y^#., Yan, Liming^#., Yu, C^#., Guo, X., Zhou, X., Hu, X., Huang, X., Rao, Z*., Lou, Z*., and Hu, J*. (2016). Structures of human mitofusin 1 provide insight into mitochondrial tethering. J Cell Biol 215, 621-629.

12.Yao, R., Ming, Z., Yan, Liming., Li, S., Wang, F., Ma, S., Yu, C., Yang, M., Chen, L., Chen, L., Li, Y., Yan, C., Miao, D., Sun, Z., Yan, J., Sun, Y., Wang, L., Chu, J., Fan, S., He, W., Deng, H., Nan, F., Li, J., Rao, Z*., Lou, Z*., and Xie, D*. (2016). DWARF14 is a non-canonical hormone receptor for strigolactone. Nature 536, 469-473.

13.Ming, Z^#., Wang, W^#., Xie, Y., Ding, P., Chen, Y., Jin, D., Sun, Y., Xia, B., Yan, Liming*., and Lou, Z*. (2014). Crystal structure of the novel di-nucleotide cyclase from Vibrio cholerae (DncV) responsible for synthesizing a hybrid cyclic GMP-AMP. Cell Res 24, 1270-1273.

14.Ren, Z^#., Yan, Liming^#., Zhang, N., Guo, Y., Yang, C., Lou, Z., and Rao, Z*. (2013). The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease. Protein Cell 4, 248-250.

15.Yan, Liming^#., Ma, Y., Liu, D., Wei, X., Sun, Y., Chen, X., Zhao, H., Zhou, J., Wang, Z*., Shui, W*., and Lou, Z*. (2012). Structural basis for the impact of phosphorylation on the activation of plant receptor-like kinase BAK1. Cell Res 22, 1304-1308.

16.Yan, Liming^#., Ma, Y^#., Sun, Y., Gao, J., Chen, X., Liu, J., Wang, C., Rao, Z., and Lou, Z*. (2011). Structural basis for mechanochemical role of Arabidopsis thaliana dynamin-related protein in membrane fission. J Mol Cell Biol 3, 378-381.

Complete list of publications: https://www.researchgate.net/profile/Yan-Liming/research