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| Content Provider | Springer Nature Link |
|---|---|
| Author | Choi, Moonju Lee, Sungjin Choi, Taekyu Lee, Choongho |
| Copyright Year | 2013 |
| Abstract | 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. |
| Starting Page | 395 |
| Ending Page | 407 |
| Page Count | 13 |
| File Format | |
| ISSN | 09208569 |
| Journal | Virus Genes |
| Volume Number | 47 |
| Issue Number | 3 |
| e-ISSN | 1572994X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2013-07-19 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Hepatitis C virus RNA genome replication Amphipathic helix NS4B dimerization/multimerization NS4B subcellular localization NS4B inhibitor Anguizole Mechanism of action NS5A Medical Microbiology Virology Plant Sciences |
| Content Type | Text |
| Resource Type | Article |
| Subject | Virology Genetics Medicine Molecular Biology |
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