Nuclear import inhibitor N-(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection.

Autor: Wang C; Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800, Australia., Yang SNY; Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800, Australia., Smith K; School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia., Forwood JK; School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia., Jans DA; Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800, Australia. Electronic address: David.Jans@monash.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Dec 02; Vol. 493 (4), pp. 1555-1559. Date of Electronic Publication: 2017 Oct 04.
DOI: 10.1016/j.bbrc.2017.10.016
Abstrakt: In the absence of approved therapeutics, Zika virus (ZIKV)'s recent prolific outbreaks in the Americas, together with impacts on unborn fetuses of infected mothers, make it a pressing human health concern worldwide. Although a key player in viral replication in the infected host cell cytoplasm, ZIKV non-structural protein 5 (NS5) appears to contribute integrally to pathogenesis by localising in the host cell nucleus, in similar fashion to NS5 from Dengue virus (DENV). We show here for the first time that ZIKV NS5 is recognized with high nanomolar affinity by the host cell importin α/β1 heterodimer, and that this interaction can be blocked by the novel DENV NS5 targeting inhibitor N-(4-hydroxyphenyl) retinamide (4-HPR). Importantly, we show that 4-HPR has potent anti-ZIKV activity at low μM concentrations. With an established safety profile for human use, 4-HPR represents an exciting possibility as an anti-ZIKV agent.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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