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

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 h...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2017-05, Vol.60 (9), p.3533-3551
Main Authors: Ju, Han, Zhang, Jian, Huang, Boshi, Kang, Dongwei, Huang, Bing, Liu, Xinyong, Zhan, Peng
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - pharmacology
Crystallography, X-Ray
Dogs
Endonucleases - antagonists & inhibitors
Endonucleases - chemistry
Endonucleases - metabolism
Enzyme Inhibitors - pharmacology
Influenza A Virus, H1N1 Subtype - enzymology
Madin Darby Canine Kidney Cells
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.6b01227