钱朝晖课题组
各实验室介绍
钱朝晖课题组成立于2014年，现有课题组长（研究员）1人，副研究员1人，助理研究员1人，技术人员2人，博士后1人，在读博士4人，在读硕士1人以及联合培养学生和聘用人员，共14人。本课题组主要从事冠状病毒入侵和感染机制的相关研究。先后承担多项国家重点研发专项、国家自然科学基金、北京市自然科学基金和中国医学科学院医学与健康创新工程项目等。近年来以通讯作者或者共同通讯作者在Cell Discovery, Nat Communications, National Science Review, Science Bulletin, Cellular and Molecular Immunology, Advanced Science, PLos Pathogens, Journal of Virology等本领域高水平杂志发表SCI论文十多篇，申请和授权专利4项。
主要研究成果
1.冠状病毒入侵机制方面：首次发现了人冠状病毒HKU1 S蛋白受体结合区，解析了其结构并发现中和抗体和受体结合关键位点（Journal of Virology 2015, Nature Communications 2017）；发现了β冠状病毒的膜融合肽，阐明了冠状病毒的模式病毒-小鼠肝炎病毒S蛋白跟其受体结合启动自身的构象变化的机制，提出了病毒S蛋白的稳定性和病毒的适应性的新关系 (Journal of Virology 2016, 2018, 2019)；最早独立发现新冠病毒受体为人ACE2和可溶性ACE2可作为抑制新冠入侵的潜在药物的团队之一，最早报道了内吞途径是新冠病毒入侵宿主细胞的主要方式之一以及COVID-19和SARS康复期病人的血清之间仅具有有限的交叉保护作用 (Nature Communications 2020)，论文它引超过3000次（Google Scholar），入选中国科学技术信息研究所2021年度“中国百篇最具影响国际学术论文”。
2.蝙蝠冠状病毒跨种传播机制研究：首次报道了中菊头蝠ACE2是蝙蝠冠状病毒RaTG13的受体，较系统地评估了蝙蝠冠状病毒RaTG13、BANAL-20-52和BANAL-20-236的潜在跨种感染能力，发现RaTG13和BANAL病毒具有潜在跨种传播风险，但现有新冠疫苗可能对其具有保护作用；另外，首次发现粪口途径传播对蝙蝠冠状病毒S蛋白的结构和功能存在重要影响。
课题组发表文章如下：
(1) Xiuyuan Ou#, Ge Xu#, Pei Li#, Yan Liu#, Fuwen Zan, Pan Liu, Jiaxin Hu, Xing Lu, Siwen Dong, Yao Zhou, Zhixia Mu, Zhiqiang Wu, Jianwei Wang, Qi Jin, Pinghuang Liu, Jian Lu, Xiangxi Wang*, Zhaohui Qian* Host susceptibility and structural and immunological insight of S proteins of two SARS-CoV-2 closely related bat coronaviruses. Cell Discovery 9:78, 2023 通讯作者
(2) Xinkai Wu,#, Kejia Shan,#, Fuwen Zan,#, Xiaolu Tang, Zhaohui Qian*, Jian Lu* Optimization and deoptimization of codons in SARS-CoV-2 and the implications for vaccine development. Advanced Science, 02 June, 2023 https://doi.org/10.1002/advs.202205445 (2023) (共同通讯作者)
(3) Mengqi Yuan, Yanzhi Zhu, Guanlan Liu, Yujie Wang, Guanxi Wang, Guozhong Zhang, Lilin Ye, Zhaohui Qian* and Pinghuang Liu* An RBD bispecific antibody effectively neutralizes a SARS?CoV?2 Omicron variant. One Health Advance, 1:12 (2023) (共同通讯作者)
(4) Xiaolu Tang, Zhaohui Qian, Xuemei Lu, Jian Lu. Adaptive evolution of the Spike protein in coronaviruses. Molecular Biology and Evolution, 2023, msad089. doi: 10.1093/molbev/msad089. (2023)
(5) Siqi He, Jiali Wang, Hanyi Chen, Zhaohui Qian, Keping Hu, Bingjie Shi, Jianxun Wang, A Competitive Panning Method Reveals an Anti-SARS-CoV-2 Nanobody Specific for an RBD-ACE2 Binding Site. Vaccines (Basel), 6;11(2):371. doi: 10.3390/vaccines11020371. (2023)
(6) Donglan Liu, Chunke Chen, Dingbin Chen, Airu Zhu, Fang Li, Zhen Zhuang, Chris Ka Pun Mok, Jun Dai, Xiaobo Li, Yingkang Jin, Zhao Chen, Jing Sun, Yanqun Wang, Yuming Li, Yanjun Zhang, Liyan Wen, Zhaoyong Zhang, Jianfen Zhuo, Junxiang Wang, Wei Ran, Dong Wang, Shengnan Zhang, Yanhong Tang, Suxiang Li, Xiaoming Lai, Peilan Wei, Jinwei Yuan, Fangli Chen, Shuxiang Huang, Fangfang Sun, Zhaohui Qian, Wenjie Tan, Jingxian Zhao, Malik Peiris, Jincun Zhao. Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2, Proc Natl Acad Sci U S A . 2023 Jan 24;120(4):e2202820120. doi: 10.1073/pnas.2202820120. Epub 2023 Jan 18.
(7) Pei Li#, Jiaxin Hu#, Yan Liu#, Xiuyuan Ou, Zhixia Mu, Xing Lu, Fuwen Zan, Mengmeng Cao, Lin Tan, Siwen Dong, Yao Zhou, Jian Lu, Qi Jin, Jianwei Wang, Zhiqiang Wu*, Yingtao Zhang*, Zhaohui Qian* Effect of polymorphism in Rhinolophus affinis ACE2 on entry of SARS-CoV-2 related bat coronaviruses. Plos Pathogens, 2023 19(1):e1011116 (通讯作者)
(8) Zhiqiang Wu # *, Yelin Han#, Yuyang Wang #, Bo Liu#, Lamei Zhao#, Junpeng Zhang, Haoxiang Su, Wenliang Zhao, Liguo Liu, Shibin Bai, Jie Dong, Lilian Sun, Yafang Zhu, Siyu Zhou, Yiping Song, Hongtao Sui, Jian Yang, Jianwei Wang, Shuyi Zhang*, Zhaohui Qian*, Qi Jin* A comprehensive survey of bat sarbecoviruses across China in relation to the origins of SARS-CoV and SARS-CoV-2. National Science Review, 2022 nwac213, https://doi.org/10.1093/nsr/nwac213 (共同通讯作者)
(9) Dan Mi, Jiaxin Hu, Zhaohui Qian. A lentiviral pseudotype system to characterize SARS-CoV-2 glycoprotein. Methods in Molecular Biology 2610:187-199. doi: 10.1007/978-1-0716-2895-9_16 (2023) (通讯作者)
(10) Xiuyuan Ou, Zhaohui Qian. Characterization of SARS-CoV-2 glycoprotein using a quantitative cell-cell fusion system. Methods in Molecular Biology 2610:179-186. doi: 10.1007/978-1-0716-2895-9_15 (2023) (通讯作者)
(11) Aurelio Bonavia，Samuel R. Dominguez，Gabriela Dveksler, Sara Gagneten, Megan Howard, Scott Jeffers, Zhaohui Qian, Mary Kathryn Smith, Larissa B. Thackray, Dina B. Tresnan, David E. Wentworth, David R. Wessner, Richard K. Williams, and Tanya A. Miura Kathryn V. Holmes: A Career of Contributions to the Coronavirus Field. Viruses 2022, 14(7), 1573
(12) Dan Wu , Ying Ye , Lin Tang , Ai-Bin Wang , Rui Zhang , Zhao-Hui Qian, Fu-Zhen Wang , Hui Zheng , Chang Huang , Xiao-Ya Lv, Hai-Feng Wang, Yan-Yang Zhang , Jing-Jing Pan , Ya-Fei Li , Ming-Xia Lu , Chang-Shuang Wang , Ya-Ting Ma , Zhi-Jie An, Lance Everett Rodewald , Zun-Dong Yin , Xuan-Yi Wang , Zhi-Yin Wu , Yi-Ming Shao. A Case-Case Study on the Effect of Primary and Booster immunization with China-produced COVID-19 Vaccines on Prevention of Pneumonia and Viral Load among Vaccinated Persons infected by Delta and Omicron Variants. Emerg Microbes Infect. 2022 Jul 19;1-15. doi: 10.1080/22221751.2022.2103455
(13) Mengqi Yuan, Xiangyu Chen, Yanzhi Zhu, Xiaoqing Dong, Yan Liu, Zhaohui Qian*, Lilin Ye*, and Pinghuang Liu*. A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern. Journal of Virology, 2022，96(16):e0077522. doi: 10.1128/jvi.00775-22 (共同通讯作者)
(14) Zhaohui Qian*, Pei Li, Xiaolu Tang, Jian Lu*. Evolutionary dynamics of the severe acute respiratory syndrome coronavirus 2 genomes. Medical Review, 2022，2(1): 3-22 (第一作者和共同通讯作者)
(15) Xiaoli Zhao, Xiaomin Ma, John H Dupius, Ruxi Qi, Jenny Jingxin Tian, Jiaxin Chen, Xiuyuan Ou, Zhaohui Qian, Dehai Liang, Peiyi Wang, Rickey Y Yada, Shenlin Wang. Negatively charged phospholipids accelerate the membrane fusion activity of the plant-specific insert domain of an aspartic protease. Journal of Biological Chemistry, 298(1):101430. doi: 10.1016/j.jbc.2021.101430. (2022)
(16) Kun Yue, Bin Yao , Yingchao Shi , Yang Yang, Zhaohui Qian , Yali Ci , Lei Shi. The stalk domain of SARS-CoV-2 NSP13 is essential for its helicase activity. Biochem Biophys Res Commun 601:129-136. doi: 10.1016/j.bbrc.2022.02.068, (2022)
(17) Chung-I Wu, Haijun Wen, Jian Lu, Xiao-Dong Su, Alice C Hughes, Weiwei Zhai, Chen Chen, Hua Chen, Mingkun Li, Shuhui Song, Zhaohui Qian, Qihui Wang, Bingjie Chen, Zixiao Guo, Yongsen Ruan, Xuemei Lu, Fuwen Wei, Li Jin, Le Kang, Yongbiao Xue, Guoping Zhao, Ya-Ping Zhang. On the origin of SARS-CoV-2-The blind watchmaker argument. Sci China Life Sci 64(9):1560-1563. doi: 10.1007/s11427-021-1972-1. (2021)
(18) Zhiqiang Wu, Qi Jin, Guizhen Wu, Jian Lu, Mingkun Li, Deyin Guo, Ke Lan, Luzhao Feng, Zhaohui Qian, Lili Ren, Wenjie Tan, Wenbo Xu, Weizhong Yang, Jianwei Wang, Chen Wang. SARS-CoV-2's origin should be investigated worldwide for pandemic prevention. Lancet, 398(10308):1299-1303. doi: 10.1016/S0140-6736(21)02020-1. (2021)
(19) Pei Li#, Ruixuan Guo#, Yan Liu#, Yingtao Zhang#, Jiaxin Hu, Xiuyuan Ou, Dan Mi, Ting Chen, Zhixia Mu, Yelin Han, Zihan Chen, Zewei Cui, Leiliang Zhang, Xinquan Wang, Zhiqiang Wu*, Jianwei Wang*, Qi Jin*, Zhaohui Qian* The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2 . Science Bulletin, 2021 Jun 30; 66(12):1215-1227. （通讯作者）
(20) Xiaoli Zhao, Jenny Jingxin Tian, Hua Yu, Brian C Bryksa, John H Dupuis, Xiuyuan Ou, Zhaohui Qian, Chen Song, Shenlin Wang, Rickey Y Yada，Insights into the mechanism of membrane fusion induced by the plant defense element, Plant Specific Insert. Journal of Biological Chemistry, doi: 10.1074/jbc.RA120.014311, 2020
(21) Xiaolu Tang, Changcheng Wu, Xiang Li, Yuhe Song, Xinmin Yao, Xinkai Wu, Yuange Duan, Hong Zhang, Yirong Wang, Zhaohui Qian, Jie Cui*, Jian Lu* On the origin and continuing evolution of SARS-CoV-2. National Science Review, Nwaa036, 2020. (ESI高被引)
(22) Xiangyu Chen, Ren Li, Zhiwei Pan, Chunfang Qian, Yang Yang, Renrong You, Jing Zhao, Pinghuang Liu, Leiqiong Gao, Zhirong Li, Qizhao Huang, Lifan Xu, Jianfang Tang, Qin Tian, Wei Yao， Li Hu, Xiaofeng Yan, Xinyuan Zhou, Yuzhang Wu,Kai Deng, Zheng Zhang, Zhaohui Qian*, Yaokai Chen* and Lilin Ye* Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor. Cellular & Molecular Immunology, 17：647–649 (2020) (共同通讯作者, Google Scholar引用>300)
(23) Xiuyuan Ou*, Yan Liu*, Xiaobo Lei*, Pei Li, Dan Mi, Lili Ren, Li Guo, Ruixuan Guo, Ting Chen, Jiaxing Hu, Zichun Xiang, Zhixia Mu, Xing Chen, Jieyong Chen, Keping Hu, Qi Jin#, Jianwei Wang#, Zhaohui Qian#，Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Comms. 2020 Mar 27; 11(1):1620 (通讯作者，Google Scholar引用>2,800，ESI高被引, F1000, 入选中国科学技术信息研究所 2021 年“中国百篇最具影响国际学术论文”,入选Nat Comm杂志COVID-19 collection, 为NC杂志新冠论文引用数最高论文)
(24) Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T, Jiang YZ, Xiong Y, Li YJ, Li H, Fan GH, Gu XY, Xiao Y, Gao H, Xu JY, Yang F, Wang XM, Wu C, Chen L, Liu YW, Liu B, Yang J, Wang XR, Dong J, Li L, Huang CL, Zhao JP, Hu Y, Cheng ZS, Liu LL, Qian ZH, Qin C, Jin Q, Cao B, Wang JW，Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J (Engl). 2020 Jan 30. doi: 10.1097/CM9. 00722 . (2020) (ESI高被引)
(25) Yiman Geng,# Haiqing Yan#, Pei Li, Gaixian Ren, Xiaopeng Guo, Pei Yin, Lu Zhang, Zhaohui Qian*, Zhengdong Zhao*, Yicheng Sun*, A highly efficient in vivo plasmid editing tool based on CRISPR-Cas12a and phage λ Red recombineering. J Genet Genomics. S1673-8527(19)30147-X. (共同通讯作者)
(26) Dan Mi&, Xiuyuan Ou&, Pei Li, Guiqing Peng, Yan Liu, Ruixuan Guo, Zhixia Mu, Fang Li, Kathryn Holmes, and Zhaohui Qian, Glycine 29 is critical for conformational changes of spike glycoprotein of MHV-A59 triggered by either receptor binding or high pH. Journal of Virology, 93(20). pii: e01046-19. (2019) (通讯作者)
(27) Pei Li#, Yiwei Shan#, Wangliang Zheng, Xiuyuan Ou, Dan Mi, Zhixia Mu, Kathryn V Holmes, Zhaohui Qian*. Identification of H209 essential for pH 8-triggered receptor-independent syncytium formation by S protein of MHV-A59, Journal of Virology, 92(11): e00209-18. (2018) (通讯作者)
(28) Xiuyuan Ou#, Hongxing Guan#, Bo Qin, Zhixia Mu, Justyna Wojdyla, Meitian Wang, Samuel R. Dominguez, Zhaohui Qian* and Sheng Cui*, Crystal Structure of the Receptor Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1. Nat Comm. May 23;8:15216 （2017）(共同通讯作者)
(29) Guiqing Peng #, Yang Yang #, Joseph R. Pasquarella, Liqing Xu, Zhaohui Qian, Kathryn V. Holmes, and Fang Li, Molecular Mechanism for Coronavirus-driven Evolution of Mouse Receptor, Journal of Biological Chemistry, 2017, 292(6):2174-2181.
(30) Xiuyuan Ou#, Wangliang Zhen#, Yiwei Shan, Zhixia Mu, Samuel R. Dominguez, Kathryn V. Holmes, Zhaohui Qian*, Identification of the Fusion Peptide-Containing Region in Betacoronavirus Spike Glycoproteins, Journal of Virology, 2016, 90(12):5586-600. （通讯作者）
(31) Zhiqiang Wu#, Li Yang#, Xianwen Ren#, Guimei He#, Junpeng Zhang, Jian Yang, Zhaohui Qian, Jie Dong, Lilian Sun, Yafang Zhu, Jiang Du, Fan Yang, Shuyi Zhang*, and Qi Jin*. Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases. The ISME Journal, 2016, 10(3):609-20.
(32) Zhiqing Jiang, Lajos Gera, Colin T. Mant, Brooke Hirsch, Zhe Yan, Zhaohui Qian, Kathryn V. Holmes, Jonathan A. Shortt, David D. Pollock, Robert S. Hodges, Platform technology to generate broadly cross-reactive antibodies to α-helical epitopes in hemagglutinin proteins from influenza a viruses. Biopolymer. 2016
(33) Zhaohui Qian#*, Xiuyuan Ou#, Luiz Gustavo Bentim Góes, Christina Osborne, Anna Castano, Kathryn V. Holmes, and Samuel R. Dominguez*. Identification of the Receptor Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1.” Journal of Virology, 2015, 89(17):8816-8827. (共同第一作者和通讯作者)