title: Synthesis and Metabolic Studies of Host Directed Inhibitors for Anti Viral Therapy.
abstract: Targeting host cell factors required for virus replication provides an alternative to targeting pathogen components and represents a promising approach to develop broad-spectrum antiviral therapeutics. High-throughput screening (HTS) identified two classes of inhibitors (2and3) with broad-spectrum antiviral activity against ortho- and paramyxoviruses including influenza A virus (IAV), measles virus (MeV), respiratory syncytial virus (RSV), and human parainfluenza virus type 3 (HPIV3). Hit-to-lead optimization delivered inhibitor,28a, with EC50values of 0.88 and 0.81 μM against IAV strain WSN and MeV strain Edmonston, respectively. It was also found that compound28adelivers good stability in human liver S9 fractions with a half-life of 165 minutes. These data establish28aas a promising lead for antiviral therapy through a host-directed mechanism.
authors: Emory Institute for Drug Development, Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd., NE Atlanta, GA 30329, USA.
authors: Terry W
authors: TW
authors: Moore
authors: Kasinath
authors: K
authors: Sana
authors: Dan
authors: D
authors: Yan
authors: Stefanie A
authors: SA
authors: Krumm
authors: Pahk
authors: P
authors: Thepchatri
authors: James P
authors: JP
authors: Snyder
authors: José
authors: J
authors: Marengo
authors: Richard F
authors: RF
authors: Arrendale
authors: Andrew J
authors: AJ
authors: Prussia
authors: Michael G
authors: MG
authors: Natchus
authors: Dennis C
authors: DC
authors: Liotta
authors: Richard K
authors: RK
authors: Plemper
authors: Aiming
authors: A
authors: Sun
keywords: Myxovirus inhibitor; benzimidazole; host-directed; influenza A; metabolic stability; respiratory syncytial virus
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