title: Identification, synthesis, and evaluation of new neuraminidase inhibitors.
abstract: High-throughput screening was performed on ∼6800 compounds to identify KR-72039 as an inhibitor of H1N1 and H5N1 neuraminidases (NAs). Structure-activity relationship studies led to 3e, which inhibited H5N1 NA with an IC50 of 2.8 μM and blocked viral replication. Docking analysis shows that compounds bind to loop-430 around the NA active site. Compound 3l additionally inhibited H7N9 NA, making it a dual inhibitor of N1- and N2-type NAs.
authors.affiliation: Taiwan International Graduate Program, Academia Sinica , Taipei 115, Taiwan.
authors.forename: Vathan
authors.initials: V
authors.lastname: Kumar
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Chang
authors.forename: Kian-Pin
authors.initials: KP
authors.lastname: Tan
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Jung
authors.forename: Shih-Hsun
authors.initials: SH
authors.lastname: Chen
authors.forename: Yih-Shyun E
authors.initials: YS
authors.lastname: Cheng
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Liang
mesh_terms: D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000593342:KR-72039; D011720:Pyrazoles; D009439:Neuraminidase