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Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives

文献类型： 外文期刊

作者： Ju, Han 1 ; Zhang, Jian 1 ; Huang, Boshi 1 ; Kang, Dongwei 1 ; Huang, Bing 2 ; Liu, Xinyong 1 ; Zhan, Peng 1 ;

作者机构： 1.Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China

2.Shandong Acad Agr Sci, Poultry Inst, 1 Jiaoxiao Rd, Jinan 250023, Shandong, Peoples R China

期刊名称：JOURNAL OF MEDICINAL CHEMISTRY （ 影响因子：7.446； 五年影响因子：7.319 ）

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收录情况： SCI

摘要： Influenza virus (IFV) causes periodic global influenza pandemics, resulting in substantial socioeconomic loss and burden on medical facilities. Yearly variation in the effectiveness of vaccines, slow responsiveness to vaccination in cases of pandemic IFV, and emerging resistance to available drugs highlight the need to develop additional small-molecular inhibitors that act on IFV proteins. One promising target: is polymerase acidic (PA) endonuclease, which is a bridged dinuclear metalloenzyme that plays a crucial role in initiating IFV replication. During the past decade, intensive efforts have been made to develop small-molecular inhibitors of his endonuclease as candidate agents for treatment of IFV infection. Here, we review the current status of development of PA endonuclease inhibitors and we discuss the applicability of newer medicinal-chemistry strategies for the discovery more potent, selective, and safer inhibitors.

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