tetano
Editor, Senior Moderator
Virology. 2017 Apr 8;507:32-39. doi: 10.1016/j.virol.2017.04.001. [Epub ahead of print]
[h=1]Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.[/h] Chutiwitoonchai N[SUP]1[/SUP], Mano T[SUP]1[/SUP], Kakisaka M[SUP]1[/SUP], Sato H[SUP]1[/SUP], Kondoh Y[SUP]2[/SUP], Osada H[SUP]2[/SUP], Kotani O[SUP]3[/SUP], Yokoyama M[SUP]3[/SUP], Sato H[SUP]3[/SUP], Aida Y[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function.
Copyright ? 2017 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Chromosome region maintenance 1; Influenza A virus; Nuclear export protein; Nuclear export signal; Nucleoprotein
PMID: 28399435 DOI: 10.1016/j.virol.2017.04.001
[h=1]Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.[/h] Chutiwitoonchai N[SUP]1[/SUP], Mano T[SUP]1[/SUP], Kakisaka M[SUP]1[/SUP], Sato H[SUP]1[/SUP], Kondoh Y[SUP]2[/SUP], Osada H[SUP]2[/SUP], Kotani O[SUP]3[/SUP], Yokoyama M[SUP]3[/SUP], Sato H[SUP]3[/SUP], Aida Y[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function.
Copyright ? 2017 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Chromosome region maintenance 1; Influenza A virus; Nuclear export protein; Nuclear export signal; Nucleoprotein
PMID: 28399435 DOI: 10.1016/j.virol.2017.04.001