4MDS : Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and non-covalent nanomolar inhibitors with an induced-fit binding

Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.6
Classification:HYDROLASE/HYDROLASE INHIBITOR
Release Date:2013-10-02
Deposition Date:2013-08-23
Revision Date:2013-10-16#2013-11-06
Molecular Weight:34144.06
Macromolecule Type:Protein
Residue Count:303
Atom Site Count:2426
DOI:10.2210/pdb4mds/pdb

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.