Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element

No Thumbnail Available
Authors
Kankanamalage, 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
Advisors
Issue Date
2018-04-25
Type
Article
Keywords
MERS-CoV , 3CL protease , Piperidine moiety , Antiviral , Peptidomimetic inhibitors
Research Projects
Organizational Units
Journal Issue
Citation
Kankanamalage, 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 334-346
Abstract

There 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.

Table of Contents
Description
Click on the DOI link to access the article (may not be free).
Publisher
Elsevier
Journal
Book Title
Series
European Journal of Medicinal Chemistry;v.150
PubMed ID
DOI
ISSN
0223-5234
EISSN