Structure-guided design and optimization of dipeptidyl inhibitors of norovirus 3CL protease. Structure-activity relationships and biochemical, X-ray crystallographic, cell-based, and in vivo studies

Journal of Medicinal Chemistry
Anushka C Galasiti KankanamalageWilliam C Groutas

Abstract

Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of antinorovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection.

References

Apr 28, 1968·Journal of Molecular Biology·B W Matthews
Apr 20, 1967·Biochemical and Biophysical Research Communications·I Schechter, A Berger
Oct 27, 1995·Journal of Medicinal Chemistry·D V PatelE W Petrillo
Apr 1, 1997·Nature Structural Biology·K Diederichs, P A Karplus
Jul 4, 2001·The Journal of Biological Chemistry·C C TaggartN G McElvaney
Oct 25, 2001·The Journal of Organic Chemistry·Douglas P. KjellMichael J. Semo
Apr 23, 2003·Virology·Susan J BlakeneyPatricia A Reilly
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Liz PottertonMartin Noble
Feb 16, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Scott A ThorntonXi Jiang
Dec 22, 2005·Acta Crystallographica. Section D, Biological Crystallography·Philip Evans
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans
Jul 1, 2011·Journal of Medicinal Chemistry·Preetpal Singh SidhuUmesh R Desai
Aug 2, 2011·Bioorganic & Medicinal Chemistry Letters·Kok-Chuan TiewWilliam C Groutas
Sep 7, 2011·Bioorganic & Medicinal Chemistry·Dengfeng DouWilliam C Groutas
Nov 9, 2011·European Journal of Medicinal Chemistry·Dengfeng DouWilliam C Groutas
Nov 29, 2011·Bioorganic & Medicinal Chemistry Letters·Dengfeng DouWilliam C Groutas
Feb 24, 2012·Bioorganic & Medicinal Chemistry·Dengfeng DouWilliam C Groutas
Apr 3, 2012·Expert Opinion on Drug Discovery·Yunxiang LuWeiliang Zhu
May 26, 2012·Science·P Andrew Karplus, Kay Diederichs
Jun 16, 2012·Bioorganic & Medicinal Chemistry Letters·Sivakoteswara Rao MandadapuWilliam C Groutas
Nov 30, 2012·The New England Journal of Medicine·Karin Bok, Kim Y Green
Dec 12, 2012·Bioorganic & Medicinal Chemistry Letters·Sivakoteswara Rao MandadapuWilliam C Groutas
Dec 12, 2012·Protein Science : a Publication of the Protein Society·Matthew R ScholfieldP Shing Ho
Jun 4, 2013·Bioorganic & Medicinal Chemistry Letters·Sivakoteswara Rao MandadapuWilliam C Groutas
Jul 10, 2013·Journal of Food Protection·Grace TungLee-Ann Jaykus
Sep 24, 2013·Bioorganic & Medicinal Chemistry Letters·Sivakoteswara Rao MandadapuWilliam C Groutas
Sep 24, 2013·Virus Research·Daisuke TakahashiKyeong-Ok Chang
Oct 16, 2013·Bioorganic & Medicinal Chemistry Letters·Allan M PriorDuy H Hua
Nov 10, 2013·Future Microbiology·Armando AriasIan Goodfellow
Nov 16, 2013·Current Opinion in Gastroenterology·Sasirekha RamaniMary K Estes
Nov 19, 2013·The Journal of General Virology·Lucy G Thorne, Ian G Goodfellow
Mar 4, 2014·Antiviral Research·Stuart S KaufmanBrent E Korba
May 13, 2014·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·L BarclayB Lopman
Jun 4, 2014·Biochemical Pharmacology·Joana Rocha-PereiraDirk Jochmans
Aug 8, 2014·Current Opinion in Infectious Diseases·Miren Iturriza-Gómara, Benjamin Lopman

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Citations

Jan 30, 2016·Journal of Medicinal Chemistry·Vishnu C DamalankaWilliam C Groutas
Aug 11, 2015·Journal of Medicinal Chemistry·Yunjeong KimWilliam C Groutas
Apr 26, 2016·Expert Opinion on Drug Discovery·Sahani WeerasekaraDuy H Hua
Jun 20, 2016·Current Opinion in Virology·Bv Venkataram PrasadRobert L Atmar
Oct 21, 2016·Current Opinion in Pharmacology·Marcella BassettoAndrea Brancale
Jul 4, 2017·Journal of Medicinal Chemistry·Anushka C Galasiti KankanamalageKyeong-Ok Chang
Feb 18, 2016·Expert Opinion on Therapeutic Patents·Anushka C Galasiti KankanamalageWilliam C Groutas
Jan 26, 2018·PloS One·Hsing-I HuangJhao-Yin Lin
Dec 26, 2018·Medicinal Research Reviews·Natalie E NetzlerPeter A White
Aug 5, 2020·Science Translational Medicine·Athri D RathnayakeKyeong-Ok Chang
Mar 3, 2019·Viruses·Kyeong-Ok ChangWilliam C Groutas
Dec 4, 2016·European Journal of Medicinal Chemistry·Anushka C Galasiti KankanamalageWilliam C Groutas
Aug 4, 2020·Journal of Structural Biology: X·Jingxu GuoFrank von Delft
Oct 22, 2018·Antiviral Research·Krishani Dinali PereraYunjeong Kim
Mar 16, 2018·European Journal of Medicinal Chemistry·Anushka C Galasiti KankanamalageWilliam C Groutas
Dec 31, 2016·European Journal of Medicinal Chemistry·Vishnu C DamalankaWilliam C Groutas
Dec 12, 2017·European Journal of Medicinal Chemistry·Vishnu C DamalankaWilliam C Groutas
Apr 26, 2021·Journal of Molecular Biology·Elena ArutyunovaM Joanne Lemieux
Jul 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Chamandi S DampallaKyeong-Ok Chang
Sep 19, 2020·Journal of Medicinal Chemistry·Athri D RathnayakeWilliam C Groutas

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