2002 Fiscal Year Final Research Report Summary
DRUG DESIGINS OF INHIBITORS TARGETED TO REPLICASE AND REPLICATION OF HEPATITIS C VIRUS (HCV)
| Project/Area Number |
12558084
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Molecular biology
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
MURAKAMI Seishi Kanazawa University, Dept. Mol. Oncology, Cancer Res. Inst., Professor, がん研究所, 教授 (90019878)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUSAKAWA Takashi Hokutokagakusangyou,Resaercher, 研究員
HAYASHI Naoyuki Kanazawa University, Dept. Mol. Oncology, Cancer Res. Insti., Research Associate., がん研究所, 助手 (50253456)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Keywords | HCV NS5B / RNA dependent RNA polymerase (RdRP) / Alanine scanning / HCV replication / NS5A / Template / primer binding / Oligomerization / Nucleolin |
|---|
| Research Abstract |
As inhibition of HCV replication is expected to reduce or even block incidence of HCV-associated hepatocellular carcinoma, HCV NS5B, aRNA-dependent RNA polymerase, might be a strong target for drug designs to inhibit HCV replication. The main results are followings. 1) 5 residues of NS5B were newly identified to be critical for RNA-dependent RNA synthesis (RdRP) activity. 2)Two residues among them located far from the RdRP catalytic center were specified to be indispensable ones for oligomerization of NS5B. The oligomerization of NS5B was found to be prerequisite to RdRP activity of NS5B by demonstrating that the two residues are residue-specific and exchangeable for oligomerization and RdRP activities. 3)Specific interaction between NS5A and NS5B was characterized, and we found that NS5A can modulate RdRP activity through the direct interaction in vitro. 4) Nucleolin, was found to bind directly to NS5B and affected subcellular localization of NS5B when the C-terminal membrane-attachment domain was truncated. These interaction surfaces of NS5B would be putative targets for drug designs to inhibit HCV replication.
|
