Mechanistic Study of Compound CGU-V001against Influenza Virus

• Main Authors: Tzu Yi Chen, 陳子宜
• Other Authors: J. T. Horng
• Format: Others
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/55556056787676469399

碩士 === 長庚大學 === 生物醫學研究所 === 101 === Influenza virus is an important pathogen that causes high morbidity and mortality worldwide. The newly emerged high lethality drug resistant swine-origin influenza A (H1N1) virus in 2009 causes thread of pandemic alarm. Due to economic lost and extensive morbidity and mortality by influenza viruses, more and more measures available to control such pathogens are ongoing. This study was aimed to investigate the antiviral mechanism of a chemical compound CGU-V001. CGU-V001 exhibited inhibitory activity against enteroviruses and influenza viruses. CGU-V001 inhibited influenza viruses with 50% inhibitory concentrations in the range of 7.6 –89.6 µM in MDCK cells, measured by neutralization assay with no cytotoxic effect. However, it didn’t inhibit B/TW/70325/05, adenovirus, and HSV-1. We found out that CGU-V001 did not inhibit influenza infection at late stage according to the results of time of addition assay. We also observed that CGU-V001 treatment resulted in a decreases M1 RNA expression but without significantly affecting M1 protein and viral polymerase activity. Besides, it did not target to hemagglutinin or neuraminidase. We further investigate whether CGU-V001 affect viral protein distribution or HA maturation, but our results shown that it did not exert its efficacy at neither these stages. At last, we found that it directly reduced pAKT level, which was induced by virus infection. The results obtained in this study suggested that CGU-V001 could be a potential drug lead against influenza. Further investigation on how CGU-V001 affecting AKT signaling pathway is required to fully understand the mechanism of it.