| Autor: |
Vannakambadi K. Ganesh, Radhakrishnan Padmanabhan, Sukathida Ubol, Nagarajan Pattabiraman, Ratree Takhampunya, Changsuek Yon, E Reichert, Y Kono, B Falgout, Tadahisa Teramoto, Krishna H. M. Murthy, Niklaus H. Mueller |
| Rok vydání: |
2008 |
| Předmět: |
|
| Zdroj: |
New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277 |
| DOI: |
10.1002/0470058005.ch6 |
| Popis: |
Dengue viruses (DENV) have 5'-capped RNA genomes of (+) polarity and encode a single polyprotein precursor that is processed into mature viral proteins. NS2B, NS3 and NS5 proteins catalyse/activate enzyme activities that are required for key processes in the virus life cycle. The heterodimeric NS2B/NS3 is a serine protease required for processing. Using a high-throughput protease assay, we screened a small molecule chemical library and identified -200 compounds having > or = 50% inhibition. Moreover, NS3 exhibits RNA-stimulated NTPase, RNA helicase and the 5'-RNA triphosphatase activities. The NTPase and the 5'-RTPase activities of NS3 are stimulated by interaction with NS5. Moreover, the conserved, positively charged motif in DENV-2 NS3, 184RKRK, is required for RNA binding and modulates the RNA-dependent enzyme activities of NS3. To study viral replication, a variety of methods are used such as the in vitro RNA-dependent RNA polymerase assays that utilize lysates from DENV-2-infected mosquito or mammalian cells or the purified NS5 along with exogenous short subgenomic viral RNAs or the replicative intracellular membrane-bound viral RNAs as templates. In addition, a cell-based DENV-2 replicon RNA encoding a luciferase reporter is also used to examine the role of cis-acting elements within the 3' UTR and the RKRK motif in viral replication. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
