Bioorganic & Medicinal Chemistry Letters
Volume 23, Issue 22, 15 November 2013, Pages 6172-6177
Mark Turlington, Aspen Chun, Sakshi Tomar, Aimee Eggler, Valerie Grum-Tokars, Jon Jacobs, J. Scott Daniels, Eric Dawson, Adrian Saldanha, Peter Chase, Yahira M. Baez-Santos, Craig W. Lindsley, Peter Hodder, Andrew D. Mesecar, Shaun R. Stauffer
Abstract
Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2–S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond.
Keywords
3CLpro, Severe acute respiratory syndrome, SARS, MERS, Coronavirus