skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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:
 [1];  [2];  [1];  [3];  [4];  [5];  [4];  [2];  [1]
  1. Wichita State Univ., KS (United States)
  2. Kansas State Univ., Manhattan, KS (United States)
  3. LiS Consulting, Lawrence, KS (United States)
  4. Univ. of Kansas, Lawrence, KS (United States)
  5. 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. doi: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. doi: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. doi: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}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 4 works
Citation information provided by
Web of Science

Save / Share:

Works referencing / citing this record:

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
  • DOI: 10.1002/med.21545

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
  • DOI: 10.1039/c9md00234k

Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors
journal, February 2019

  • Chang, Kyeong-Ok; Kim, Yunjeong; Lovell, Scott
  • Viruses, Vol. 11, Issue 2
  • DOI: 10.3390/v11020197