PMID- 28399435
OWN - NLM
STAT- MEDLINE
DCOM- 20170717
LR  - 20231213
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 507
DP  - 2017 Jul
TI  - Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and 
      nuclear export protein as a novel target for antiviral drug development.
PG  - 32-39
LID - S0042-6822(17)30102-2 [pii]
LID - 10.1016/j.virol.2017.04.001 [doi]
AB  - 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Chutiwitoonchai, Nopporn
AU  - Chutiwitoonchai N
AD  - Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, 
      Japan.
FAU - Mano, Takafumi
AU  - Mano T
AD  - Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, 
      Japan.
FAU - Kakisaka, Michinori
AU  - Kakisaka M
AD  - Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, 
      Japan.
FAU - Sato, Hirotaka
AU  - Sato H
AD  - Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, 
      Japan.
FAU - Kondoh, Yasumitsu
AU  - Kondoh Y
AD  - Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 
      2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Osada, Hiroyuki
AU  - Osada H
AD  - Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 
      2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
FAU - Kotani, Osamu
AU  - Kotani O
AD  - Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of 
      Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
FAU - Yokoyama, Masaru
AU  - Yokoyama M
AD  - Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of 
      Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
FAU - Sato, Hironori
AU  - Sato H
AD  - Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of 
      Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
FAU - Aida, Yoko
AU  - Aida Y
AD  - Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, 
      Japan. Electronic address: aida@riken.jp.
LA  - eng
GR  - U58 DP002392/DP/NCCDPHP CDC HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170408
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Antiviral Agents)
RN  - 0 (Karyopherins)
RN  - 0 (Nucleoproteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Antiviral Agents/pharmacology
MH  - Cell Line
MH  - Cell Nucleus/metabolism/virology
MH  - Humans
MH  - Influenza A virus/genetics/*metabolism
MH  - Influenza, Human/*metabolism/virology
MH  - Karyopherins/antagonists & inhibitors/genetics/*metabolism
MH  - Nucleoproteins/genetics/*metabolism
MH  - Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors/genetics/*metabolism
MH  - Exportin 1 Protein
PMC - PMC7111614
OTO - NOTNLM
OT  - Chromosome region maintenance 1
OT  - Influenza A virus
OT  - Nuclear export protein
OT  - Nuclear export signal
OT  - Nucleoprotein
EDAT- 2017/04/12 06:00
MHDA- 2017/07/18 06:00
PMCR- 2017/04/08
CRDT- 2017/04/12 06:00
PHST- 2016/11/30 00:00 [received]
PHST- 2017/03/31 00:00 [revised]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/04/12 06:00 [pubmed]
PHST- 2017/07/18 06:00 [medline]
PHST- 2017/04/12 06:00 [entrez]
PHST- 2017/04/08 00:00 [pmc-release]
AID - S0042-6822(17)30102-2 [pii]
AID - 10.1016/j.virol.2017.04.001 [doi]
PST - ppublish
SO  - Virology. 2017 Jul;507:32-39. doi: 10.1016/j.virol.2017.04.001. Epub 2017 Apr 8.