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- W4360616213 abstract "Enterovirus infections have become a serious public health threat to young children, leading to hand-foot-and-mouth disease and more severe nervous system diseases. Due to the lack of licensed anti enterovirus drugs, we reported herein that a Tenovin-1 analog, acylthiourea-based 4-(tert-butyl)-N-((4-(4-(tert-butyl)benzamido)phenyl)carbamothioyl) benzamide (AcTU), displayed low nanomolar anti-EV-A71 activity with an EC50 of 1.0 nM in RD cells. Moreover, AcTU exhibited nanomolar to picomolar inhibitory activity against a series of enteroviruses including EV-D68, CV-A21, CV-A16 and CV-B1 (EC50 = 0.75-17.15 nM). Mechanistic studies indicated that AcTU inhibited enterovirus proliferation by targeting 3D polymerase. In addition, AcTU displayed moderate pharmacokinetic properties in rats (F = 7.4%, T1/2 = 3.26 h), and in vivo protection studies demonstrated that AcTU orally administered at 0.6 mg/kg/d was highly protective against lethal EV-A71 challenge in mice, potentially reducing mortality from 100% to 20% as well as alleviating symptoms. These results suggested that AcTU could be a potent clinical candidate for the treatment of enterovirus infections." @default.
- W4360616213 created "2023-03-24" @default.
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- W4360616213 date "2023-05-01" @default.
- W4360616213 modified "2023-10-18" @default.
- W4360616213 title "Identification of a novel acylthiourea-based potent broad-spectrum inhibitor for enterovirus 3D polymerase in vitro and in vivo" @default.
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- W4360616213 doi "https://doi.org/10.1016/j.antiviral.2023.105583" @default.
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