tetano
Editor, Senior Moderator
J Med Chem. 2017 Jan 24. doi: 10.1021/acs.jmedchem.6b01227. [Epub ahead of print]
[h=1]Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives.[/h] Ju H, Zhang J, Huang B, Kang D, Huang B, Liu X, Zhan P.
[h=3]Abstract[/h] Influenza virus (IFV) causes periodic global influenza pandemics, resulting in substantial socio-economic 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.
PMID: 28118010 DOI: 10.1021/acs.jmedchem.6b01227
[PubMed - as supplied by publisher]
[h=1]Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives.[/h] Ju H, Zhang J, Huang B, Kang D, Huang B, Liu X, Zhan P.
[h=3]Abstract[/h] Influenza virus (IFV) causes periodic global influenza pandemics, resulting in substantial socio-economic 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.
PMID: 28118010 DOI: 10.1021/acs.jmedchem.6b01227
[PubMed - as supplied by publisher]