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Title: Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease

Abstract

Abstract not provided.

Authors:
; ORCiD logo; ; ; ; ; ; ; ORCiD logo;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1462573
Resource Type:
Journal Article
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Beylkin, Diane, Kumar, Gyanendra, Zhou, Wei, Park, Jaehyeon, Jeevan, Trushar, Lagisetti, Chandraiah, Harfoot, Rhodri, Webby, Richard J., White, Stephen W., and Webb, Thomas R. Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease. United States: N. p., 2017. Web. doi:10.1038/s41598-017-17419-6.
Beylkin, Diane, Kumar, Gyanendra, Zhou, Wei, Park, Jaehyeon, Jeevan, Trushar, Lagisetti, Chandraiah, Harfoot, Rhodri, Webby, Richard J., White, Stephen W., & Webb, Thomas R. Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease. United States. doi:10.1038/s41598-017-17419-6.
Beylkin, Diane, Kumar, Gyanendra, Zhou, Wei, Park, Jaehyeon, Jeevan, Trushar, Lagisetti, Chandraiah, Harfoot, Rhodri, Webby, Richard J., White, Stephen W., and Webb, Thomas R. Fri . "Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease". United States. doi:10.1038/s41598-017-17419-6.
@article{osti_1462573,
title = {Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease},
author = {Beylkin, Diane and Kumar, Gyanendra and Zhou, Wei and Park, Jaehyeon and Jeevan, Trushar and Lagisetti, Chandraiah and Harfoot, Rhodri and Webby, Richard J. and White, Stephen W. and Webb, Thomas R.},
abstractNote = {Abstract not provided.},
doi = {10.1038/s41598-017-17419-6},
journal = {Scientific Reports},
issn = {2045-2322},
number = 1,
volume = 7,
place = {United States},
year = {2017},
month = {12}
}

Works referenced in this record:

Dihydroxypyrimidine-4-carboxamides as Novel Potent and Selective HIV Integrase Inhibitors
journal, May 2007

  • Pace, Paola; Di Francesco, M. Emilia; Gardelli, Cristina
  • Journal of Medicinal Chemistry, Vol. 50, Issue 9
  • DOI: 10.1021/jm070027u

The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit
journal, February 2009

  • Dias, Alexandre; Bouvier, Denis; Crépin, Thibaut
  • Nature, Vol. 458, Issue 7240
  • DOI: 10.1038/nature07745

Global Mortality Impact of the 1957–1959 Influenza Pandemic
journal, February 2016

  • Viboud, Cécile; Simonsen, Lone; Fuentes, Rodrigo
  • Journal of Infectious Diseases, Vol. 213, Issue 5
  • DOI: 10.1093/infdis/jiv534

Structural Analysis of Specific Metal Chelating Inhibitor Binding to the Endonuclease Domain of Influenza pH1N1 (2009) Polymerase
journal, August 2012


Multinational Impact of the 1968 Hong Kong Influenza Pandemic: Evidence for a Smoldering Pandemic
journal, July 2005

  • Viboud, Cécile; Grais, Rebecca F.; Lafont, Bernard A. P.
  • The Journal of Infectious Diseases, Vol. 192, Issue 2
  • DOI: 10.1086/431150

Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997

  • Murshudov, G. N.; Vagin, A. A.; Dodson, E. J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3
  • DOI: 10.1107/S0907444996012255

Crystallographic Fragment Screening and Structure-Based Optimization Yields a New Class of Influenza Endonuclease Inhibitors
journal, September 2013

  • Bauman, Joseph D.; Patel, Disha; Baker, Steven F.
  • ACS Chemical Biology, Vol. 8, Issue 11
  • DOI: 10.1021/cb400400j

Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the PA Endonuclease
journal, August 2012


Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor
journal, March 2016

  • Song, Min-Suk; Kumar, Gyanendra; Shadrick, William R.
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 13
  • DOI: 10.1073/pnas.1519772113

Crystal structure of the RNA-dependent RNA polymerase from influenza C virus
journal, October 2015

  • Hengrung, Narin; El Omari, Kamel; Serna Martin, Itziar
  • Nature, Vol. 527, Issue 7576
  • DOI: 10.1038/nature15525

Identification of Influenza Endonuclease Inhibitors Using a Novel Fluorescence Polarization Assay
journal, January 2012

  • Baughman, Brandi M.; Jake Slavish, P.; DuBois, Rebecca M.
  • ACS Chemical Biology, Vol. 7, Issue 3
  • DOI: 10.1021/cb200439z

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

Discovery of Raltegravir, a Potent, Selective Orally Bioavailable HIV-Integrase Inhibitor for the Treatment of HIV-AIDS Infection
journal, September 2008

  • Summa, Vincenzo; Petrocchi, Alessia; Bonelli, Fabio
  • Journal of Medicinal Chemistry, Vol. 51, Issue 18
  • DOI: 10.1021/jm800245z

Phenyl Substituted 4-Hydroxypyridazin-3(2 H )-ones and 5-Hydroxypyrimidin-4(3 H )-ones: Inhibitors of Influenza A Endonuclease
journal, September 2014

  • Sagong, Hye Yeon; Bauman, Joseph D.; Patel, Disha
  • Journal of Medicinal Chemistry, Vol. 57, Issue 19
  • DOI: 10.1021/jm500958x

Fragment-Based Identification of Influenza Endonuclease Inhibitors
journal, June 2016


Antivirals for influenza: Historical perspectives and lessons learned
journal, September 2006


Discovery and Synthesis of HIV Integrase Inhibitors:  Development of Potent and Orally Bioavailable N-Methyl Pyrimidones
journal, October 2007

  • Gardelli, Cristina; Nizi, Emanuela; Muraglia, Ester
  • Journal of Medicinal Chemistry, Vol. 50, Issue 20
  • DOI: 10.1021/jm0704705

Synthesis of Natural Flutimide and Analogous Fully Substituted Pyrazine-2,6-diones, Endonuclease Inhibitors of Influenza Virus
journal, August 2001

  • Singh, Sheo B.; Tomassini, Joanne E.
  • The Journal of Organic Chemistry, Vol. 66, Issue 16
  • DOI: 10.1021/jo015665d


journal, December 2007


Structure of influenza A polymerase bound to the viral RNA promoter
journal, November 2014

  • Pflug, Alexander; Guilligay, Delphine; Reich, Stefan
  • Nature, Vol. 516, Issue 7531
  • DOI: 10.1038/nature14008

PA subunit of RNA polymerase as a promising target for anti-influenza virus agents
journal, June 2008


Two Distinctive Binding Modes of Endonuclease Inhibitors to the N-Terminal Region of Influenza Virus Polymerase Acidic Subunit
journal, April 2016


Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus
journal, December 2001

  • Taubenberger, Jeffery K.; Reid, Ann H.; Janczewski, Thomas A.
  • Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, Vol. 356, Issue 1416
  • DOI: 10.1098/rstb.2001.1020

Favipiravir: A New Medication for the Ebola Virus Disease Pandemic
journal, December 2014

  • Nagata, Takashi; Lefor, Alan K.; Hasegawa, Manabu
  • Disaster Medicine and Public Health Preparedness, Vol. 9, Issue 1
  • DOI: 10.1017/dmp.2014.151

3-Hydroxyquinolin-2(1 H )-ones As Inhibitors of Influenza A Endonuclease
journal, May 2013

  • Sagong, Hye Yeon; Parhi, Ajit; Bauman, Joseph D.
  • ACS Medicinal Chemistry Letters, Vol. 4, Issue 6
  • DOI: 10.1021/ml4001112

Use of a Pharmacophore Model To Discover a New Class of Influenza Endonuclease Inhibitors
journal, March 2003

  • Parkes, Kevin E. B.; Ermert, Philipp; Fässler, Jürg
  • Journal of Medicinal Chemistry, Vol. 46, Issue 7
  • DOI: 10.1021/jm020334u

The 1918 Spanish influenza:integrating history and biology
journal, January 2001


Structural and computational study on inhibitory compounds for endonuclease activity of influenza virus polymerase
journal, September 2015

  • Fudo, Satoshi; Yamamoto, Norio; Nukaga, Michiyoshi
  • Bioorganic & Medicinal Chemistry, Vol. 23, Issue 17
  • DOI: 10.1016/j.bmc.2015.07.046

Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2
journal, July 2014

  • Clark, Michael P.; Ledeboer, Mark W.; Davies, Ioana
  • Journal of Medicinal Chemistry, Vol. 57, Issue 15
  • DOI: 10.1021/jm5007275

N-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile metal binding modes
journal, August 2016

  • Carcelli, Mauro; Rogolino, Dominga; Gatti, Anna
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep31500

Current and novel antiviral strategies for influenza infection
journal, June 2016


Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds.
journal, December 1994

  • Tomassini, J.; Selnick, H.; Davies, M. E.
  • Antimicrobial Agents and Chemotherapy, Vol. 38, Issue 12
  • DOI: 10.1128/AAC.38.12.2827

Crystal structure of an avian influenza polymerase PAN reveals an endonuclease active site
journal, February 2009

  • Yuan, Puwei; Bartlam, Mark; Lou, Zhiyong
  • Nature, Vol. 458, Issue 7240
  • DOI: 10.1038/nature07720

When poor solubility becomes an issue: From early stage to proof of concept
journal, August 2007

  • Stegemann, S.; Leveiller, F.; Franchi, D.
  • European Journal of Pharmaceutical Sciences, Vol. 31, Issue 5
  • DOI: 10.1016/j.ejps.2007.05.110

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

Preclinical Activity of VX-787, a First-in-Class, Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit
journal, December 2014

  • Byrn, Randal A.; Jones, Steven M.; Bennett, Hamilton B.
  • Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 3
  • DOI: 10.1128/AAC.04623-14

2-Substituted-4,5-Dihydroxypyrimidine-6-Carboxamide Antiviral Targeted Libraries
journal, November 2009

  • Boyd, Vincent A.; Mason, John; Hanumesh, Parimala
  • Journal of Combinatorial Chemistry, Vol. 11, Issue 6
  • DOI: 10.1021/cc900111u

A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro
journal, July 2016

  • Jones, Jeremy C.; Marathe, Bindumadhav M.; Lerner, Christian
  • Antimicrobial Agents and Chemotherapy, Vol. 60, Issue 9
  • DOI: 10.1128/AAC.00888-16


journal, October 2014


Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives
journal, February 2017