title: Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives.
abstract: 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 this 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.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , 44, West Culture Road, 250012, Jinan, Shandong, P. R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Ju
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , 44, West Culture Road, 250012, Jinan, Shandong, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , 44, West Culture Road, 250012, Jinan, Shandong, P. R. China.
authors.forename: Boshi
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , 44, West Culture Road, 250012, Jinan, Shandong, P. R. China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Kang
authors.affiliation: Poultry Institute, Shandong Academy of Agricultural Sciences , 1, Jiaoxiao Road, 250023, Jinan, Shandong, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , 44, West Culture Road, 250012, Jinan, Shandong, P. R. China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , 44, West Culture Road, 250012, Jinan, Shandong, P. R. China.
authors.forename: Peng
authors.identifier: 0000-0002-9675-6026
authors.initials: P
authors.lastname: Zhan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004285:Dogs; D004720:Endonucleases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology*; D061985:Madin Darby Canine Kidney Cells
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D004720:Endonucleases