Structure-based design of a novel inhibitor of the ZIKA virus NS2B/ NS3 protease
文献类型：期刊论文
| 作者 | Xiong, Yanchao3,4,5; Cheng, Fei4,5; Zhang, Junyi4,5; Su, Haixia4,5; Hu, Hangchen2; Zou, Yi4,5; Li, Minjun1; Xu, Yechun2,3,4,5
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| 刊名 | BIOORGANIC CHEMISTRY
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| 出版日期 | 2022-11-01 |
| 卷号 | 128页码:7 |
| 关键词 | Zika virus Fragment -based hit screening Protein -inhibitor interactions NS2B NS3 protease Crystal structure |
| ISSN号 | 0045-2068 |
| DOI | 10.1016/j.bioorg.2022.106109 |
| 通讯作者 | Li, Minjun(liminjun@sinap.ac.cn) ; Xu, Yechun(ycxu@simm.ac.cn) |
| 英文摘要 | Zika virus (ZIKV) has been a serious public health problem, and there is no vaccine or drug approved for the prevention or treatment of ZIKV yet. The ZIKV NS2B/NS3 protease plays an important role in processing the virus precursor polyprotein and is thus a promising target for antiviral drugs development. In order to discover novel inhibitors of this protease, we carried out a fragment-based hit screening and characterized protein -inhibitor interactions using the X-ray crystallography together with isothermal titration calorimetry. We re-ported two high-resolution crystal structures of the protease (bZiProC143S) in complex with an active fragment as well as a tetrapeptide, revealing that there is domain swapping in the protein structures and two ligands only occupy the substrate-binding pocket of one copy in a symmetric unit. Based on the detailed binding modes of two ligands revealed by crystal structures, we designed a novel inhibitor which inhibits the NS2B/NS3 protease with a higher potency than the fragment and possesses a higher ligand-binding efficiency and a comparable IC50 compared to the tetrapeptide. These results thus provide a structural basis and valuable hint for development of more potent inhibitors of the ZIKV NS2B/NS3 protease.
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| WOS关键词 | NS2B-NS3 PROTEASE ; ANTIVIRAL ACTIVITY ; ALLOSTERIC INHIBITORS ; CRYSTAL-STRUCTURE ; BROAD-SPECTRUM ; POTENT ; DRUG ; DISCOVERY ; INFECTION |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000859890600002 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302649]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Minjun; Xu, Yechun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai Synchrotron Radiat Facil, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Zhejiang, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiong, Yanchao,Cheng, Fei,Zhang, Junyi,et al. Structure-based design of a novel inhibitor of the ZIKA virus NS2B/ NS3 protease[J]. BIOORGANIC CHEMISTRY,2022,128:7. |
| APA | Xiong, Yanchao.,Cheng, Fei.,Zhang, Junyi.,Su, Haixia.,Hu, Hangchen.,...&Xu, Yechun.(2022).Structure-based design of a novel inhibitor of the ZIKA virus NS2B/ NS3 protease.BIOORGANIC CHEMISTRY,128,7. |
| MLA | Xiong, Yanchao,et al."Structure-based design of a novel inhibitor of the ZIKA virus NS2B/ NS3 protease".BIOORGANIC CHEMISTRY 128(2022):7. |
入库方式： OAI收割
来源：上海药物研究所
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