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Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins

文献类型： 外文期刊

作者： Hou, Lingxin 1 ; Zhang, Ying 1 ; Ju, Han 1 ; Cherukupalli, Srinivasulu 1 ; Jia, Ruifang 1 ; Zhang, Jian 5 ; Huang, Bing 2 ; Loregian, Arianna 3 ; Liu, Xinyong 1 ; Zhan, Peng 1 ;

作者机构： 1.Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Dept Med Chem,Key Lab Chem Biol,Minist Educ, Jinan 250012, Peoples R China

2.Shandong Acad Agr Sci, Inst Poultry Sci, Jinan 250100, Peoples R China

3.Univ Padua, Dept Mol Med, I-35121 Padua, Italy

4.China Belgium Collaborat Res Ctr Innovat Antivira, Jinan 250012, Peoples R China

5.Shandong Univ, Hosp 2, Cheeloo Coll Med, Inst Med Sci, Jinan 250033, Peoples R China

关键词： Influenza virus; Drug design; Influenza polymerase; Ribonucleoprotein complex; Medicinal-chemistry strategies

期刊名称：ACTA PHARMACEUTICA SINICA B （ 影响因子：14.903； 五年影响因子：12.905 ）

ISSN： 2211-3835

年卷期： 2022 年 12 卷 4 期

页码：

收录情况： SCI

摘要： Influenza is an acute respiratory infectious disease caused by the influenza virus, affecting people globally and causing significant social and economic losses. Due to the inevitable limitations of vaccines and approved drugs, there is an urgent need to discover new anti-influenza drugs with different mechanisms. The viral ribonucleoprotein complex (vRNP) plays an essential role in the life cycle of influenza viruses, representing an attractive target for drug design. In recent years, the functional area of constituent proteins in vRNP are widely used as targets for drug discovery, especially the PA endonuclease active site, the RNA-binding site of PB1, the cap-binding site of PB2 and the nuclear export signal of NP protein. Encouragingly, the PA inhibitor baloxavir has been marketed in Japan and the United States, and several drug candidates have also entered clinical trials, such as favipiravir. This article reviews the compositions and functions of the influenza virus vRNP and the research progress on vRNP inhibitors, and discusses the representative drug discovery and optimization strategies pursued. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

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