PMID- 23868571
OWN - NLM
STAT- MEDLINE
DCOM- 20140615
LR  - 20220817
IS  - 1572-994X (Electronic)
IS  - 0920-8569 (Linking)
VI  - 47
IP  - 3
DP  - 2013 Dec
TI  - A hepatitis C virus NS4B inhibitor suppresses viral genome replication by 
      disrupting NS4B's dimerization/multimerization as well as its interaction with 
      NS5A.
PG  - 395-407
LID - 10.1007/s11262-013-0956-5 [doi]
AB  - Chronic hepatitis C virus (HCV) infection is responsible for severe liver 
      diseases including liver cirrhosis and hepatocellular carcinoma. An HCV 
      non-structural protein 4B (NS4B) plays an essential role in viral RNA genome 
      replication by building multi-vesicular structures around endoplasmic reticulum 
      membranes. Especially, the second amphipathic helix of NS4B (NS4B-AH2) was shown 
      to be essential for this process. By screening compounds against a 
      membrane-aggregating activity of NS4B-AH2, several anti-HCV replication small 
      molecules targeting NS4B-AH2 were discovered. However, little is known about 
      detailed molecular mechanism of action for these NS4B-AH2 inhibitors. In this 
      report, we provide evidences that NS4B-AH2 is required for NS4B's 
      dimerization/multimerization, its proper subcellular localization, as well as its 
      interaction with NS5A. More importantly, one of NS4B-AH2 inhibitors called 
      "anguizole" was found to be able to disrupt all of these NS4B-AH2-mediated 
      biological functions of NS4B. This newly elucidated mechanism of action will 
      enable us not only to better understand a central role of NS4B-AH2 in HCV life 
      cycle but also to develop a more safe and effective new class of NS4B-AH2 
      inhibitors of HCV replication in the future.
FAU - Choi, Moonju
AU  - Choi M
AD  - College of Pharmacy, Dongguk University-Seoul, Goyang, 410-050, South Korea.
FAU - Lee, Sungjin
AU  - Lee S
FAU - Choi, Taekyu
AU  - Choi T
FAU - Lee, Choongho
AU  - Lee C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130719
PL  - United States
TA  - Virus Genes
JT  - Virus genes
JID - 8803967
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 2.7.7.48 (NS-5 protein, hepatitis C virus)
SB  - IM
MH  - Dimerization
MH  - Genome, Viral
MH  - Hepacivirus/chemistry/genetics/*physiology
MH  - Hepatitis C/*virology
MH  - Humans
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Viral Nonstructural Proteins/*chemistry/genetics/*metabolism
MH  - *Virus Replication
EDAT- 2013/07/23 06:00
MHDA- 2014/06/16 06:00
CRDT- 2013/07/23 06:00
PHST- 2013/03/22 00:00 [received]
PHST- 2013/07/08 00:00 [accepted]
PHST- 2013/07/23 06:00 [entrez]
PHST- 2013/07/23 06:00 [pubmed]
PHST- 2014/06/16 06:00 [medline]
AID - 10.1007/s11262-013-0956-5 [doi]
PST - ppublish
SO  - Virus Genes. 2013 Dec;47(3):395-407. doi: 10.1007/s11262-013-0956-5. Epub 2013 
      Jul 19.