Inhibitory effect of diphyllin, a vacuolar ATPase blocker, on feline infectious peritonitis virus

• Main Authors: Wei-Shan Chang, 張維珊
• Other Authors: Hui-Wen Chen
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/89747595076843353043

碩士 === 國立臺灣大學 === 獸醫學研究所 === 105 === Abstract Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. So far, it remains incurable, and there is no effective vaccine commercially available. The compound diphyllin, a novel vacuolar ATPase blocker, has been shown to inhibit the intracellular endosomal acidification, thus interfering the infection of influenza virus and dengue virus. This study aims to investigate the antiviral activity of diphyllin against the type II feline infectious peritonitis virus (FIPV) strain NTU156. The results show that diphyllin dose-dependently inhibited endosomal acidification in Fcwf-4 cells. Treatment with diphyllin altered the cellular susceptibility to FIPV and inhibited the downstream virus replication. Furthermore, combinatorial treatment of the host-targeting diphyllin with pathogen-targeting Galanthus nivalis agglutinin demonstrated enhanced cell protection. In the in vitro model of antibody-dependent enhancement of FIPV infection, diphyllin also showed a significant antiviral activity against FIPV in Fcwf-4 cells and U937 cells. In addition, nanoparticulate diphyllin further demonstrated a decreased cytotoxicity and improved inhibitory effect against FIPV. These results collectively suggest that diphyllin possesses therapeutic potential for the treatment of FIP. Keywords: Feline infectious peritonitis virus, Diphyllin, Vacuolar ATPase inhibitor, Antibody-dependent enhancement, Nanoparticles