博士，深圳国家感染性疾病临床医学研究中心研究员。

研究方向

微生物学、结构生物学、药物开发。主要聚焦于结核分枝杆菌、冠状病毒等病原微生物关键靶标蛋白的结构、功能研究，以及相应的药物筛选和设计开发工作。主要学术成就如下：

（1） 结合X射线晶体学技术和冷冻电镜技术在国际上首先解析了分枝杆菌阿拉伯糖基转移酶复合体EmbA-EmbB-AcpM2和EmbC2-AcpM2的“药靶-药物”三维结构，揭示了一线抗结核药物乙胺丁醇作用于该靶点的精确分子机制，为解决结核病耐药问题，研发新型抗结核药物奠定了重要基础。该研究成果于2020年4月发表在Science杂志上，被Nature Reviews Microbiology列为Research Highlights，入选中国医学科学院《中国2020年度重要医学进展》。

（2）利用X射线晶体学衍射技术先后解析了新型冠状病毒主蛋白酶Mpro和抗癌药物卡莫氟（Carmofur）的复合物晶体结构，以及新冠病毒主蛋白酶和辉瑞公司开发的新冠病毒治疗药物奈玛特韦（Nirmatrelvir, PF-07321332）的复合物晶体结构，揭示了两个上市药物抑制新冠病毒的精确作用机制。相关研究成果分别发表在Nature Structural & Molecular Biology和Protein & Cell杂志上。

（3）解析新型冠状病毒主蛋白酶在静息态、结合底物中间态状和切割后状态的高分辨率晶体结构，以拍“全息照片”的方式精确地揭示了主蛋白酶催化底物水解的整个过程。本研究首次系统地报道了新冠病毒主蛋白酶的底物识别特异性和催化机制，为设计更加高效的抗新冠病毒药物奠定了重要的结构基础。该论文研究成果发表在Proceedings of the National Academy of Sciences杂志上。

（4）基于荧光共振能量转移技术设计开发了针对新型冠状病毒木瓜蛋白酶PLpro的高通量药物筛选系统，从包括成药库、临床药物库以及天然活性产物库在内的6000多个化合物分子中筛选获得4个先导化合物——丹参酮、隐丹参酮、GRL0617、YM155。进一步通过X射线晶体学衍射技术解析了PLpro和临床药物YM155的高分辨率复合物结构，从原子层面上阐释了其抑制机理，为针对YM155的进一步改构提供了结构基础，更为针对冠状病毒的药物研发提供了重要理论依据。该论文研究成果发表在Protein & Cell杂志上。

代表性论著：

1. Zhao, Yao*#; Zhu, Yan*; Liu, Xiang*; Jin, Zhenming; Duan, Yinkai; Zhang, Qi; Wu, Chengyao; Feng, Lu; Du, Xiaoyu; Zhao, Jinyi; Shao, Maolin; Zhang, Bing; Yang, Xiuna; Wu, Lijie; Ji, Xiaoyun; Guddat, Luke W.; Yang, Kailin#; Rao, Zihe#; Yang, Haitao#, Structural basis for replicase polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2, Proceedings of the National Academy of Sciences, 2022, 119(16): e2117142119.

2. Zhao, Yao*; Fang, Chao*; Zhang, Qi*; Zhang, Ruxue; Zhao, Xiangbo; Duan, Yinkai; Wang, Haofeng; Zhu, Yan; Feng, Lu; Zhao, Jinyi; Shao, Maolin; Yang, Xiuna; Zhang, Leike; Peng, Chao; Yang, Kailin; Ma, Dawei#; Rao, Zihe#; Yang, Haitao#, Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332, Protein Cell, 2021, 0(0).

3. Zhao, Yao*; Du, Xiaoyu*; Duan, Yinkai*; Pan, Xiaoyan*; Sun, Yifang*; You, Tian*; Han, Lin*; Jin, Zhenming; Shang, Weijuan; Yu, Jing; Guo, Hangtian; Liu, Qianying; Wu, Yan; Peng, Chao; Wang, Jun; Zhu, Chenghao; Yang, Xiuna; Yang, Kailin; Lei, Ying; Guddat, Luke W.; Xu, Wenqing; Xiao, Gengfu; Sun, Lei#; Zhang, Leike#; Rao, Zihe#; Yang, Haitao#, High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors, Protein Cell, 2021, 12(1): 877–888.

4. Zhang, Lu*; Zhao, Yao*; Gao, Yan; Wu, Lijie; Gao, Ruogu; Zhang, Qi; Wang, Yinan; Wu, Chengyao; Wu, Fangyu; Gurcha, Sudagar S.; Veerapen, Natacha; Batt, Sarah M.; Zhao, Wei; Qin, Ling; Yang, Xiuna; Wang, Manfu; Zhu, Yan; Zhang, Bing; Bi, Lijun; Zhang, Xian'en; Yang, Haitao; Guddat, Luke W.; Xu, Wenqing; Wang, Quan#; Li, Jun#; Besra, Gurdyal S.#; Rao, Zihe#, Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol, Science, 2020, 368(6496): 1211-+.

5. Jin, Zhenming*; Zhao, Yao*; Sun, Yuan*; Zhang, Bing; Wang, Haofeng; Wu, Yan; Zhu, Yan; Zhu, Chen; Hu, Tianyu; Du, Xiaoyu; Duan, Yinkai; Yu, Jing; Yang, Xiaobao; Yang, Xiuna; Yang, Kailin; Liu, Xiang; Guddat, Luke W.; Xiao, Gengfu; Zhang, Leike#; Yang, Haitao#; Rao, Zihe, Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur, Nature Structural & Molecular Biology, 2020, 27(6): 529-+.

6. Wang, Zhengyuan*; Zhao, Yao*; Wang, Qingxing*; Xing, Yangfei*; Feng, Lu; Kong, Juan; Peng, Chao; Zhang, Leike#; Yang, Haitao#; Lu, Min#, Identification of proteasome and caspase inhibitors targeting SARS-CoV-2 Mpro, Signal Transduction and Targeted Therapy, 2021, 6(1): 214.

7. Zhang, Lu*; Zhao, Yao*; Gao, Ruogu*; Li, Jun; Yang, Xiuna; Gao, Yan; Zhao, Wei; Gurcha, Sudagar S.; Veerapen, Natacha; Batt, Sarah M.; Besra, Kajelle Kaur; Xu, Wenqing; Bi, Lijun; Zhang, Xian'en; Guddat, Luke W.; Yang, Haitao; Wang, Quan#; Besra, Gurdyal S.#; Rao, Zihe#, Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB2-AcpM2, Protein Cell, 2020, 11(7): 505-517.

8. Zang, Yi*; Su, Mingbo*; Wang, Qingxing*; Cheng, Xi*; Zhang, Wenru*; Zhao, Yao*; Chen, Tong; Jiang, Yingyan; Shen, Qiang; Du, Juan; Tan, Qiuxiang; Wang, Peipei; Gao, Lixin; Jin, Zhenming; Zhang, Mengmeng; Li, Cong; Zhu, Ya; Feng, Bo; Tang, Bixi; Xie, Han; Wang, Ming-Wei; Zheng, Mingyue; Pan, Xiaoyan; Yang, Haitao; Xu, Yechun; Wu, Beili; Zhang, Leike; Rao, Zihe; Yang, Xiuna#; Jiang, Hualiang#; Xiao, Gengfu#; Zhao, Qiang#; Li, Jia#, High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors, Protein Cell, 2022 Sep 28;14(1):17-27.

9. Jin, Zhenming*; Du, Xiaoyu*; Xu, Yechun*; Deng, Yongqiang*; Liu, Meiqin*; Zhao, Yao; Zhang, Bing; Li, Xiaofeng; Zhang, Leike; Peng, Chao; Duan, Yinkai; Yu, Jing; Wang, Lin; Yang, Kailin; Liu, Fengjiang; Jiang, Rendi; Yang, Xinglou; You, Tian; Liu, Xiaoce; Yang, Xiuna; Bai, Fang; Liu, Hong; Liu, Xiang; Guddat, Luke W.; Xu, Wenqing; Xiao, Gengfu; Qin, Chengfeng; Shi, Zhengli; Jiang, Hualiang#; Rao, Zihe#; Yang, Haitao#, Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors, Nature, 2020, 582(7811): 289-+.

10. Dai, Wenhao*; Zhang, Bing*; Jiang, Xia-Ming*; Su, Haixia*; Li, Jian; Zhao, Yao; Xie, Xiong; Jin, Zhenming; Peng, Jingjing; Liu, Fengjiang; Li, Chunpu; Li, You; Bai, Fang; Wang, Haofeng; Cheng, Xi; Cen, Xiaobo; Hu, Shulei; Yang, Xiuna; Wang, Jiang; Liu, Xiang; Xiao, Gengfu; Jiang, Hualiang; Rao, Zihe; Zhang, Lei-Ke#; Xu, Yechun#; Yang, Haitao#; Liu, Hong#, Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease, Science, 2020, 368(6497): 1331-+.

发明专利：

1. Haitao, YANG; Zhenming, JIN; Xiuna, YANG; Yao, ZHAO; Zihe, RAO, APPLICATION OF N-SUBSTITUTED PYRIDYL BENZISOSELENAZOLONE COMPOUND, 2021-02-23, WIPO, WOCN21077481.

2. Haitao, YANG; Zhenming, JIN; Xiuna, YANG; Yao, ZHAO; Zihe, RAO, APPLICATION OF DISULFIRAM IN CORONAVIRUS RESISTANCE, 2021-02-26, WIPO, WOCN21078185.

3. Haitao, YANG; Zhenming, JIN; Xiaoyu, DU; Yinkai, DUAN; Yao, ZHAO; Xiuna, YANG; Zihe, RAO, COMPOUND FOR TREATING AND//OR PREVENTING DISEASES CAUSED BY CORONAVIRUS AND USE THEREOF, 2021-04-29, WIPO, WOCN21090916.

4. YANG, Haitao; JIN, Zhenming; YANG, Xiuna; ZHAO, Yao; RAO, Zihe, Use of an N-substituted pyridyl benzisoselazolone compound, 2021-08-13, USA, US17402006.

5. 杨海涛; 靳振明; 杨秀娜; 赵耀; 饶子和, N-取代吡啶基苯并异硒唑酮化合物的应用, 2021-02-23, 中国, CN202180016412.2.

6. 杨海涛; 靳振明; 杨秀娜; 赵耀; 饶子和, 双硫仑在抗冠状病毒中的应用, 2021-02-26, 中国, ZL202180016668.3.

7. 杨海涛; 靳振明; 杨秀娜; 赵耀; 饶子和, 多酚类物质在抗冠状病毒中的应用, 2021-02-26, 中国, CN202110219570.X.

8. 杨海涛; 靳振明; 杜小宇; 段胤凯; 赵耀; 杨秀娜; 饶子和, 丹参提取物和醌类化合物在抗冠状病毒中的应用, 2021-04-29, 中国, 202110472690.0.

近年主持或参与的各类国家、省、市科技计划项目情况:

1. 国家自然科学基金委员会, 青年科学基金项目, 32200131, 新冠病毒主蛋白酶剪切复制酶多聚蛋白的复杂分子机制研究, 2023-01 至 2025-12, 30万元, 在研, 主持

2. 省部共建组分中药国家重点实验室, 国家重点实验室开放课题, CBCM2020105, 宣肺败毒方活性成分靶向新冠主蛋白酶的机制研究, 2021-04 至 2023-03, 12万元, 在研, 主持

3. 中华人民共和国科学技术部, 国家重点研发计划, 2020YFA0707500, 新型冠状病毒感染复制的分子机制和防控基础研究, 2020-04 至 2023-03, 1075万元, 在研, 项目骨干

4. 临港国家实验室, 国家实验室重点任务, LG202101-01-07, 抗病毒关键药靶的结构与药物发现, 2021-11 至 2022-10, 200万元, 结题, 子任务负责人

获得国家、省市级奖励情况:

1. 2021年度上海科技大学优秀员工

2. 2020年，中国医学科学院《中国2020年度重要医学进展》