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dc.contributor.authorKankanamalage, Anushka C. Galasiti
dc.contributor.authorKim, Yunjeong
dc.contributor.authorDamalanka, Vishnu C.
dc.contributor.authorRathnayake, Athri D.
dc.contributor.authorFehr, Anthony R.
dc.contributor.authorMehzabeen, Nurjahan
dc.contributor.authorBattaile, Kevin P.
dc.contributor.authorLovell, Scott
dc.contributor.authorLushington, Gerald H.
dc.contributor.authorPerlman, Stanley
dc.contributor.authorChang, Kyeong-Ok
dc.contributor.authorGroutas, William C.
dc.identifier.citationKankanamalage, Anushka C. Galasiti; Kim, Yunjeong; Damalanka, Vishnu C.; Rathnayake, Athri D.; Fehr, Anthony R.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Lushington, Gerald H.; Perlman, Stanley; Chang, Kyeong-Ok; Groutas, William C. 2018. Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element. European Journal of Medicinal Chemistry, vol. 150:pp 334-346en_US
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractThere are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography.en_US
dc.description.sponsorshipNational 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 was 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. We are grateful to Dr. Terry L. Bowlin, Microbiotix, Inc. for assistance in determining the cell-based values of compounds GC376 and GC813. The research was supported in part by grants from the National Institutes of Health (R01 AI109039 to K.O.C. and P01 AI060699 and R01 AI129269 to S. P.) and a faculty development KU Endowment Dolph Simons Award in Biomedical Sciences (W.C.G.)en_US
dc.relation.ispartofseriesEuropean Journal of Medicinal Chemistry;v.150
dc.subject3CL proteaseen_US
dc.subjectPiperidine moietyen_US
dc.subjectPeptidomimetic inhibitorsen_US
dc.titleStructure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design elementen_US
dc.rights.holder© 2018 Elsevier Masson SAS. All rights reserved.en_US

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