Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease
Abstract
Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. Furthermore, this report describes the discovery of a novel class of macrocyclic inhibitors of norovirus 3C-like protease, a cysteine protease that is essential for virus replication. SAR, structural, and biochemical studies were carried out to ascertain the effect of structure on pharmacological activity and permeability. Insights gained from these studies have laid a solid foundation for capitalizing on the therapeutic potential of the series of inhibitors described herein.
- Authors:
-
- Wichita State Univ., KS (United States)
- Kansas State Univ., Manhattan, KS (United States)
- LiS Consulting, Lawrence, KS (United States)
- Univ. of Kansas, Lawrence, KS (United States)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health; National Inst. of General Medical Sciences
- OSTI Identifier:
- 1368274
- Alternate Identifier(s):
- OSTI ID: 1416192
- Grant/Contract Number:
- AC02-06CH11357; AI109039; P30GM110761
- Resource Type:
- Accepted Manuscript
- Journal Name:
- European Journal of Medicinal Chemistry
- Additional Journal Information:
- Journal Volume: 127; Journal Issue: C; Journal ID: ISSN 0223-5234
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Macrocyclic inhibitors; Norovirus; 3CLprotease
Citation Formats
Damalanka, Vishnu C., Kim, Yunjeong, Galasiti Kankanamalage, Anushka C., Lushington, Gerald H., Mehzabeen, Nurjahan, Battaile, Kevin P., Lovell, Scott, Chang, Kyeong-Ok, and Groutas, William C.. Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease. United States: N. p., 2016.
Web. https://doi.org/10.1016/j.ejmech.2016.12.033.
Damalanka, Vishnu C., Kim, Yunjeong, Galasiti Kankanamalage, Anushka C., Lushington, Gerald H., Mehzabeen, Nurjahan, Battaile, Kevin P., Lovell, Scott, Chang, Kyeong-Ok, & Groutas, William C.. Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease. United States. https://doi.org/10.1016/j.ejmech.2016.12.033
Damalanka, Vishnu C., Kim, Yunjeong, Galasiti Kankanamalage, Anushka C., Lushington, Gerald H., Mehzabeen, Nurjahan, Battaile, Kevin P., Lovell, Scott, Chang, Kyeong-Ok, and Groutas, William C.. Wed .
"Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease". United States. https://doi.org/10.1016/j.ejmech.2016.12.033. https://www.osti.gov/servlets/purl/1368274.
@article{osti_1368274,
title = {Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease},
author = {Damalanka, Vishnu C. and Kim, Yunjeong and Galasiti Kankanamalage, Anushka C. and Lushington, Gerald H. and Mehzabeen, Nurjahan and Battaile, Kevin P. and Lovell, Scott and Chang, Kyeong-Ok and Groutas, William C.},
abstractNote = {Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. Furthermore, this report describes the discovery of a novel class of macrocyclic inhibitors of norovirus 3C-like protease, a cysteine protease that is essential for virus replication. SAR, structural, and biochemical studies were carried out to ascertain the effect of structure on pharmacological activity and permeability. Insights gained from these studies have laid a solid foundation for capitalizing on the therapeutic potential of the series of inhibitors described herein.},
doi = {10.1016/j.ejmech.2016.12.033},
journal = {European Journal of Medicinal Chemistry},
number = C,
volume = 127,
place = {United States},
year = {2016},
month = {12}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 4 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
New strains of norovirus and the mystery of viral gastroenteritis epidemics
journal, September 2013
- Lee, B. E.; Pang, X. -L.
- Canadian Medical Association Journal, Vol. 185, Issue 16
Genome of Emerging Norovirus GII.17, United States, 2014
journal, August 2015
- Parra, Gabriel I.; Green, Kim Y.
- Emerging Infectious Diseases, Vol. 21, Issue 8
Norovirus Disease in the United States
journal, August 2013
- Hall, Aron J.; Lopman, Ben A.; Payne, Daniel C.
- Emerging Infectious Diseases, Vol. 19, Issue 8
Global Economic Burden of Norovirus Gastroenteritis
journal, April 2016
- Bartsch, Sarah M.; Lopman, Benjamin A.; Ozawa, Sachiko
- PLOS ONE, Vol. 11, Issue 4
Noroviruses: epidemiology, immunity and prospects for prevention
journal, January 2015
- Pringle, Kimberly; Lopman, Benjamin; Vega, Everardo
- Future Microbiology, Vol. 10, Issue 1
Norovirus Gastroenteritis in Immunocompromised Patients
journal, November 2012
- Bok, Karin; Green, Kim Y.
- New England Journal of Medicine, Vol. 367, Issue 22
Norovirus
journal, January 2015
- Robilotti, Elizabeth; Deresinski, Stan; Pinsky, Benjamin A.
- Clinical Microbiology Reviews, Vol. 28, Issue 1
Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review
journal, September 2013
- Lanata, Claudio F.; Fischer-Walker, Christa L.; Olascoaga, Ana C.
- PLoS ONE, Vol. 8, Issue 9
Noroviruses: The Perfect Human Pathogens?
journal, May 2012
- Hall, A. J.
- Journal of Infectious Diseases, Vol. 205, Issue 11
Human Norovirus as a Foodborne Pathogen: Challenges and Developments
journal, April 2015
- Moore, Matthew D.; Goulter, Rebecca M.; Jaykus, Lee-Ann
- Annual Review of Food Science and Technology, Vol. 6, Issue 1
Recent Advances in the Discovery of Norovirus Therapeutics: Miniperspective
journal, August 2015
- Kim, Yunjeong; Galasiti Kankanamalage, Anushka C.; Chang, Kyeong-Ok
- Journal of Medicinal Chemistry, Vol. 58, Issue 24
Anti-norovirus therapeutics: a patent review (2010-2015)
journal, February 2016
- Galasiti Kankanamalage, Anushka C.; Weerawarna, Pathum M.; Kim, Yunjeong
- Expert Opinion on Therapeutic Patents, Vol. 26, Issue 3
Antiviral targets of human noroviruses
journal, June 2016
- Prasad, BV Venkataram; Shanker, Sreejesh; Muhaxhiri, Zana
- Current Opinion in Virology, Vol. 18
Current tools for norovirus drug discovery
journal, April 2016
- Weerasekara, Sahani; Prior, Allan M.; Hua, Duy H.
- Expert Opinion on Drug Discovery, Vol. 11, Issue 6
Norovirus vaccines and potential antinorovirus drugs: recent advances and future perspectives
journal, July 2015
- Kocher, Jacob; Yuan, Lijuan
- Future Virology, Vol. 10, Issue 7
Norovirus: Targets and tools in antiviral drug discovery
journal, September 2014
- Rocha-Pereira, Joana; Neyts, Johan; Jochmans, Dirk
- Biochemical Pharmacology, Vol. 91, Issue 1
Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial
journal, June 2016
- Atmar, Robert L.; Baehner, Frank; Cramer, Jakob P.
- Journal of Infectious Diseases, Vol. 214, Issue 6
Recent advances in understanding norovirus pathogenesis: Norovirus Pathogenesis
journal, May 2016
- Karst, Stephanie M.; Tibbetts, Scott A.
- Journal of Medical Virology, Vol. 88, Issue 11
A Working Model of How Noroviruses Infect the Intestine
journal, February 2015
- Karst, Stephanie M.; Wobus, Christiane E.
- PLOS Pathogens, Vol. 11, Issue 2
Norovirus gene expression and replication
journal, November 2013
- Thorne, L. G.; Goodfellow, I. G.
- Journal of General Virology, Vol. 95, Issue Pt_2
The influence of commensal bacteria on infection with enteric viruses
journal, February 2016
- Karst, Stephanie M.
- Nature Reviews Microbiology, Vol. 14, Issue 4
A Structural Study of Norovirus 3C Protease Specificity: Binding of a Designed Active Site-Directed Peptide Inhibitor
journal, January 2011
- Hussey, Robert J.; Coates, Leighton; Gill, Raj S.
- Biochemistry, Vol. 50, Issue 2
Substrate specificity of the Norwalk virus 3C-like proteinase
journal, October 2002
- Hardy, Michele E.; Crone, Tammera J.; Brower, Jessica E.
- Virus Research, Vol. 89, Issue 1
Structural Basis of Substrate Specificity and Protease Inhibition in Norwalk Virus
journal, January 2013
- Muhaxhiri, Z.; Deng, L.; Shanker, S.
- Journal of Virology, Vol. 87, Issue 8
Structural and dynamics characterization of norovirus protease: NMR Study of Norovirus Protease
journal, January 2013
- Takahashi, Daisuke; Hiromasa, Yasuaki; Kim, Yunjeong
- Protein Science, Vol. 22, Issue 3
Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases
journal, May 1994
- Allaire, Marc; Chernaia, Maia M.; Malcolm, Bruce A.
- Nature, Vol. 369, Issue 6475
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, March 2015
- Galasiti Kankanamalage, Anushka C.; Kim, Yunjeong; Weerawarna, Pathum M.
- Journal of Medicinal Chemistry, Vol. 58, Issue 7
Proteases Universally Recognize Beta Strands In Their Active Sites
journal, March 2005
- Tyndall, Joel D. A.; Nall, Tessa; Fairlie, David P.
- Chemical Reviews, Vol. 105, Issue 3
Macrocycles Mimic The Extended Peptide Conformation Recognized By Aspartic, Serine, Cysteine and Metallo Proteases
journal, July 2001
- Tyndall, Joel; Fairlie, David
- Current Medicinal Chemistry, Vol. 8, Issue 8
Improving Drug Candidates by Design: A Focus on Physicochemical Properties As a Means of Improving Compound Disposition and Safety
journal, September 2011
- Meanwell, Nicholas A.
- Chemical Research in Toxicology, Vol. 24, Issue 9
Lead discovery and optimization strategies for peptide macrocycles
journal, April 2015
- Bhat, Abhijit; Roberts, Lee R.; Dwyer, John J.
- European Journal of Medicinal Chemistry, Vol. 94
Macrocycles Are Great Cycles: Applications, Opportunities, and Challenges of Synthetic Macrocycles in Drug Discovery
journal, April 2011
- Marsault, Eric; Peterson, Mark L.
- Journal of Medicinal Chemistry, Vol. 54, Issue 7
Macrocyclic Drugs and Clinical Candidates: What Can Medicinal Chemists Learn from Their Properties?
journal, September 2013
- Giordanetto, Fabrizio; Kihlberg, Jan
- Journal of Medicinal Chemistry, Vol. 57, Issue 2
How Beyond Rule of 5 Drugs and Clinical Candidates Bind to Their Targets
journal, October 2015
- Doak, Bradley C.; Zheng, Jie; Dobritzsch, Doreen
- Journal of Medicinal Chemistry, Vol. 59, Issue 6
Cell permeability beyond the rule of 5
journal, June 2016
- Matsson, Pär; Doak, Bradley C.; Over, Björn
- Advanced Drug Delivery Reviews, Vol. 101
Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space
journal, January 2011
- Alex, Alexander; Millan, David S.; Perez, Manuel
- MedChemComm, Vol. 2, Issue 7
Probing the Physicochemical Boundaries of Cell Permeability and Oral Bioavailability in Lipophilic Macrocycles Inspired by Natural Products
journal, May 2015
- Bockus, Andrew T.; Lexa, Katrina W.; Pye, Cameron R.
- Journal of Medicinal Chemistry, Vol. 58, Issue 11
Improving the passive permeability of macrocyclic peptides: Balancing permeability with other physicochemical properties
journal, January 2015
- Thansandote, Praew; Harris, Robert M.; Dexter, Hannah L.
- Bioorganic & Medicinal Chemistry, Vol. 23, Issue 2
Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses
journal, August 2012
- Kim, Y.; Lovell, S.; Tiew, K. -C.
- Journal of Virology, Vol. 86, Issue 21
Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease
journal, February 2016
- Damalanka, Vishnu C.; Kim, Yunjeong; Alliston, Kevin R.
- Journal of Medicinal Chemistry, Vol. 59, Issue 5
Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease: Structural, biochemical, spectroscopic, and antiviral studies
journal, August 2016
- Weerawarna, Pathum M.; Kim, Yunjeong; Galasiti Kankanamalage, Anushka C.
- European Journal of Medicinal Chemistry, Vol. 119
Automatic indexing of rotation diffraction patterns
journal, February 1988
- Kabsch, W.
- Journal of Applied Crystallography, Vol. 21, Issue 1
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
Data processing and analysis with the autoPROC toolbox
journal, March 2011
- Vonrhein, Clemens; Flensburg, Claus; Keller, Peter
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
An introduction to data reduction: space-group determination, scaling and intensity statistics
journal, March 2011
- Evans, Philip R.
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
Solvent content of protein crystals
journal, April 1968
- Matthews, B. W.
- Journal of Molecular Biology, Vol. 33, Issue 2
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
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
MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009
- Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
Developments in the CCP 4 molecular-graphics project
journal, November 2004
- Potterton, Liz; McNicholas, Stuart; Krissinel, Eugene
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12
Scaling and assessment of data quality
journal, December 2005
- Evans, Philip
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
Improved R-factors for diffraction data analysis in macromolecular crystallography
journal, April 1997
- Diederichs, Kay; Karplus, P. Andrew
- Nature Structural Biology, Vol. 4, Issue 4
Global indicators of X-ray data quality
journal, April 2001
- Weiss, Manfred S.
- Journal of Applied Crystallography, Vol. 34, Issue 2
Linking Crystallographic Model and Data Quality
journal, May 2012
- Karplus, P. A.; Diederichs, K.
- Science, Vol. 336, Issue 6084
Resolving Some Old Problems in Protein Crystallography
journal, May 2012
- Evans, P.
- Science, Vol. 336, Issue 6084
Works referencing / citing this record:
Piperidine carbamate peptidomimetic inhibitors of the serine proteases HGFA, matriptase and hepsin
journal, January 2019
- Damalanka, Vishnu C.; Wildman, Scott A.; Janetka, James W.
- MedChemComm, Vol. 10, Issue 9
Norovirus antivirals: Where are we now?
journal, December 2018
- Netzler, Natalie E.; Enosi Tuipulotu, Daniel; White, Peter A.
- Medicinal Research Reviews, Vol. 39, Issue 3
Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors
journal, February 2019
- Chang, Kyeong-Ok; Kim, Yunjeong; Lovell, Scott
- Viruses, Vol. 11, Issue 2