Cell-based anti-influenza virus drug screening and mechanistic studies.
| Autor: | Tzu Yun Chu, 朱紫韻 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Influenza virus often causes much morbidity and mortality in the world. Influenza virus prophylaxis and treatment includes vaccines and anti-influenza virus drugs. There are many reports of resistance stains occurring for current clinical administration of anti-influenza virus drugs. Therefore, identification of novel anti-influenza virus drugs is more important. We screened ten thousand compounds and found a compound named BPR1P0034S0 that has anti-influenza A virus activity. In this study, we found that BPR1P0034S0 could inhibit influenza A viral replication. The 50% effective concentration of inhibition (EC50) of BPR1P0034S0 is 0.42 ± 0.11 uM as measured by plaque assay. In a time-of-addition experiment where BPR1P0034S0 was added at different stages along the viral replication cycle such as adsorption or post-absorption, antiviral activity of BPR1P0034S0 was more efficient in cells treated with the drug between 0 and 2 hours right after viral infection, implying that an early viral entry steps might be the target of BPR1P0034S0. IFA and western blot analysis showed that the viral protein was decreased when MDCK cells were treated with BPR1P0034S0. At the RNA level, we also found that viral RNA was slightly decreased in infected MDCK cells treated with BPR1P0034S0 by semi-quantification RT-PCR. These results suggest that BPR1P0034S0 might target virus at M2 protein or affect viral RNA importing to nucleus. We also tested the inhibition spectrum of BPR1P0034S0 for other virus, such as EV71, and found BPR1P0034S0 was not inhibitory for EV71. We concluded that BPR1P0034S0 potentially possess anti-influenza virus A activity. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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