title: Macrocyclic inhibitors of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus.
abstract: The design, synthesis, and in vitro evaluation of the first macrocyclic inhibitor of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus are reported. The in vitro inhibitory activity (50% effective concentration) of the macrocyclic inhibitor toward enterovirus 3C protease (CVB3 Nancy strain), and coronavirus (SARS-CoV) and norovirus 3C-like proteases, was determined to be 1.8, 15.5 and 5.1 μM, respectively.
authors.affiliation: Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
authors.forename: Sivakoteswara Rao
authors.initials: SR
authors.lastname: Mandadapu
authors.forename: Pathum M
authors.initials: PM
authors.lastname: Weerawarna
authors.forename: Allan M
authors.initials: AM
authors.lastname: Prior
authors.forename: Roxanne Adeline Z
authors.initials: RA
authors.lastname: Uy
authors.forename: Sridhar
authors.initials: S
authors.lastname: Aravapalli
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Alliston
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Lushington
authors.forename: Yunjeong
authors.initials: Y
authors.lastname: Kim
authors.forename: Duy H
authors.initials: DH
authors.lastname: Hua
authors.forename: Kyeong-Ok
authors.initials: KO
authors.lastname: Chang
authors.forename: William C
authors.initials: WC
authors.lastname: Groutas
mesh_terms: D017934:Coronavirus / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D029322:Norovirus / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010849:Picornaviridae / Q000201:enzymology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047028:Macrocyclic Compounds; D011480:Protease Inhibitors; D010447:Peptide Hydrolases