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Chin. Phys. B, 2018, Vol. 27(1): 018704    DOI: 10.1088/1674-1056/27/1/018704
Special Issue: TOPICAL REVIEW — Soft matter and biological physics
TOPICAL REVIEW—Soft matter and biological physics Prev   Next  

Mutation-induced spatial differences in neuraminidase structure and sensitivity to neuraminidase inhibitors

Zhi-wei Yang(杨志伟)1,2,3, Dong-xiao Hao(郝东晓)1, Yi-zhuo Che(车一卓)1, Jia-hui Yang(杨嘉辉)1, Lei Zhang(张磊)1, Sheng-li Zhang(张胜利)1
1 Department of Applied Physics, School of Science, Xi'an Jiaotong University, Xi'an 710049, China;
2 Department of Applied Chemistry, School of Science, Xi'an Jiaotong University, Xi'an 710049, China;
3 School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
Abstract  

Neuraminidase (NA), a major surface glycoprotein of influenza virus with well-defined active sites, is an ideal platform for the development of antiviral drugs. However, a growing number of NA mutations have drug resistance to today's inhibitors. Numerous efforts are made to explore the resistance mechanisms through understanding the structural changes in mutated NA proteins and the associated different binding profiles of inhibitors, via x-ray, nuclear magnetic resonance, electron microscopy, and molecular dynamics methods. This review presents the architectural features of mutated NA proteins, as well as the respective inhibitor sensitivities arising from these spatial differences. Finally, we summarize the resistance mechanisms of today's neuraminidase inhibitors and the outlook for the development of novel inhibitors.

Keywords:  mutation      active sites      neuraminidase      inhibitor sensitivity  
Received:  01 September 2017      Revised:  24 October 2017      Accepted manuscript online: 
PACS:  87.14.ej (Enzymes)  
  87.15.-v (Biomolecules: structure and physical properties)  
  87.15.A- (Theory, modeling, and computer simulation)  
  87.15.B- (Structure of biomolecules)  
Fund: 

Project supported by the National Natural Science Foundation of China (Grant Nos. 11374237 and 11504287), Fundamental Research Funds for the Central Universities, China, China Postdoctoral Science Foundation (Grant No. 2017M613147), and Shaanxi Province Postdoctoral Science Foundation, China.

Corresponding Authors:  Lei Zhang, Sheng-li Zhang     E-mail:  zhangleio@mail.xjtu.edu.cn;zhangsl@mail.xjtu.edu.cn

Cite this article: 

Zhi-wei Yang(杨志伟), Dong-xiao Hao(郝东晓), Yi-zhuo Che(车一卓), Jia-hui Yang(杨嘉辉), Lei Zhang(张磊), Sheng-li Zhang(张胜利) Mutation-induced spatial differences in neuraminidase structure and sensitivity to neuraminidase inhibitors 2018 Chin. Phys. B 27 018704

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