錢朝晖課題組

各實驗室介紹

課題組/研究單元介紹

錢朝晖課題組成立于2014年,現有(yǒu)課題組長(cháng)(研究員)1人,副研究員1人,助理(lǐ)研究員1人,技(jì )術人員2人,博士後1人,在讀博士4人,在讀碩士1人以及聯合培養學(xué)生和聘用(yòng)人員,共14人。本課題組主要從事冠狀病毒入侵和感染機制的相關研究。先後承擔多(duō)項國(guó)家重點研發專項、國(guó)家自然科(kē)學(xué)基金、北京市自然科(kē)學(xué)基金和中(zhōng)國(guó)醫(yī)學(xué)科(kē)學(xué)院醫(yī)學(xué)與健康創新(xīn)工(gōng)程項目等。近年來以通訊作(zuò)者或者共同通訊作(zuò)者在Cell Discovery, Nat Communications, National Science Review, Science Bulletin, Cellular and Molecular Immunology, Advanced Science, PLos Pathogens, Journal of Virology等本領域高水平雜志(zhì)發表SCI論文(wén)十多(duō)篇,申請和授權專利4項。

主要研究成果

1.冠狀病毒入侵機制方面:首次發現了人冠狀病毒HKU1 S蛋白受體(tǐ)結合區(qū),解析了其結構并發現中(zhōng)和抗體(tǐ)和受體(tǐ)結合關鍵位點(Journal of Virology 2015, Nature Communications 2017);發現了β冠狀病毒的膜融合肽,闡明了冠狀病毒的模式病毒-小(xiǎo)鼠肝炎病毒S蛋白跟其受體(tǐ)結合啓動自身的構象變化的機制,提出了病毒S蛋白的穩定性和病毒的适應性的新(xīn)關系 (Journal of Virology 2016, 2018, 2019);最早獨立發現新(xīn)冠病毒受體(tǐ)為(wèi)人ACE2和可(kě)溶性ACE2可(kě)作(zuò)為(wèi)抑制新(xīn)冠入侵的潛在藥物(wù)的團隊之一,最早報道了内吞途徑是新(xīn)冠病毒入侵宿主細胞的主要方式之一以及COVID-19和SARS康複期病人的血清之間僅具(jù)有(yǒu)有(yǒu)限的交叉保護作(zuò)用(yòng) (Nature Communications 2020),論文(wén)它引超過3000次(Google Scholar),入選中(zhōng)國(guó)科(kē)學(xué)技(jì )術信息研究所2021年度“中(zhōng)國(guó)百篇最具(jù)影響國(guó)際學(xué)術論文(wén)”。

2.蝙蝠冠狀病毒跨種傳播機制研究:首次報道了中(zhōng)菊頭蝠ACE2是蝙蝠冠狀病毒RaTG13的受體(tǐ),較系統地評估了蝙蝠冠狀病毒RaTG13、BANAL-20-52和BANAL-20-236的潛在跨種感染能(néng)力,發現RaTG13和BANAL病毒具(jù)有(yǒu)潛在跨種傳播風險,但現有(yǒu)新(xīn)冠疫苗可(kě)能(néng)對其具(jù)有(yǒu)保護作(zuò)用(yòng);另外,首次發現糞口途徑傳播對蝙蝠冠狀病毒S蛋白的結構和功能(néng)存在重要影響。

課題組發表文(wén)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 通訊作(zuò)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) (共同通訊作(zuò)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) (共同通訊作(zuò)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 (通訊作(zuò)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 (共同通訊作(zuò)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) (通訊作(zuò)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) (通訊作(zuò)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  (共同通訊作(zuò)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(zuò)者和共同通訊作(zuò)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. (通訊作(zuò)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) (共同通訊作(zuò)者, Google Scholar引用(yòng)>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 (通訊作(zuò)者,Google Scholar引用(yòng)>2,800,ESI高被引, F1000, 入選中(zhōng)國(guó)科(kē)學(xué)技(jì )術信息研究所 2021 年“中(zhōng)國(guó)百篇最具(jù)影響國(guó)際學(xué)術論文(wén)”,入選Nat Comm雜志(zhì)COVID-19 collection, 為(wèi)NC雜志(zhì)新(xīn)冠論文(wén)引用(yòng)數最高論文(wén))

(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. (共同通訊作(zuò)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) (通訊作(zuò)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) (通訊作(zuò)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)(共同通訊作(zuò)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. (通訊作(zuò)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(zuò)者和通訊作(zuò)者)