TY - JOUR
T1 - Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease
T2 - Structural, biochemical, spectroscopic, and antiviral studies
AU - Weerawarna, Pathum M.
AU - Kim, Yunjeong
AU - Kankanamalage, Anushka C.Galasiti
AU - Damalanka, Vishnu C.
AU - Lushington, Gerald H.
AU - Alliston, Kevin R.
AU - Mehzabeen, Nurjahan
AU - Battaile, Kevin P.
AU - Lovell, Scott
AU - Chang, Kyeong Ok
AU - Groutas, William C.
N1 - Funding Information:
The generous financial support of this work by the National Institutes of Health ( R01AI109039 ) is gratefully acknowledged. Use of the University of Kansas Protein Structure Laboratory was supported by a grant from the National Institute of General Medical Sciences ( P30GM110761 ) of the National Institutes of Health. Use of the IMCA-CAT beamline 17-ID at the Advanced Photon Source as supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Hauptman-Woodward Medical Research Institute . Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-06CH11357 .
PY - 2016
Y1 - 2016
N2 - Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus infections. A potentially effective strategy for the development of norovirus therapeutics entails the discovery of inhibitors of norovirus 3CL protease, an enzyme essential for noroviral replication. We describe herein the structure-based design of the first class of permeable, triazole-based macrocyclic inhibitors of norovirus 3C-like protease, as well as pertinent X-ray crystallographic, biochemical, spectroscopic, and antiviral studies.
AB - Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus infections. A potentially effective strategy for the development of norovirus therapeutics entails the discovery of inhibitors of norovirus 3CL protease, an enzyme essential for noroviral replication. We describe herein the structure-based design of the first class of permeable, triazole-based macrocyclic inhibitors of norovirus 3C-like protease, as well as pertinent X-ray crystallographic, biochemical, spectroscopic, and antiviral studies.
KW - 3CL protease
KW - Macrocyclic inhibitors
KW - Norovirus
KW - β-strand conformation
UR - https://www.scopus.com/pages/publications/84975730964
U2 - 10.1016/j.ejmech.2016.04.013
DO - 10.1016/j.ejmech.2016.04.013
M3 - Article
C2 - 27235842
AN - SCOPUS:84975730964
SN - 0223-5234
VL - 119
SP - 300
EP - 318
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -